囊泡转运的动态跟踪及其与脂筏关系的初步研究
|
摘要
细胞物质转运实质上是细胞内的一个庞大而复杂的物流系统,这一系统的异常将导致相应各种疾病的发生。囊泡是这一物流系统中的一种可调控的重要的运输工具,脂筏是膜脂双层内含有特殊脂质及蛋白质的微区,在这一物流系统中具有重要的作用。本课题引入单分子研究技术和全内反射荧光成像技术,实时动态地研究转运囊泡的动力学过程,和两类脂筏与囊泡之间的动态空间定位关系。这一研究有助于我们进一步揭示囊泡转运机制和糖尿病的发生机制,而且对于进一步认识脂筏功能及开发以GLUT4为靶的调节血糖的药物都具有重要的理论及实际指导意义。
机体内葡萄糖的平衡对生命过程至关重要。胰岛素是调节血糖平衡的重要激素,它促进葡萄糖进入细胞内,从而降低血中葡萄糖。胰岛素的这一作用是通过细胞内的葡萄糖转运体(Glucose Transporter,GLUT)家族之一葡萄糖转运子4(GLUT4)将葡萄糖从细胞外转运到细胞内的。研究表明II型糖尿病的发生与细胞内GLUT4的转运障碍有关。而GLUT4的转运被认为是受多种因素控制的,这些因素目前较公认的有GLUT4在细胞器中的保持机制、动态分选、囊泡的转运、锚定和与质膜的融合以及质膜的脂质结构。GLUT4在细胞内的转运至少有两个循环,一个是细胞表面和内涵体间的循环,一个是在trans-Golgi network (TGN) 和内涵体间的循环。在这两个循环中GLUT4转位有几个严格的控制点。这两个循环似乎告诉我们GLUT4在胞内可能有两种运动形式。为了回答这个问题,我们研究了GLUT4在胞内的动力学过程。在研究过程中使用Confocal显微镜观察了GLUT4在胞内的整体分布。使用全内反射荧光显微镜时序成像获得了GLUT4的动态连续的图像,用于三维动力学分析。分析中发展了单颗粒追踪方法(SPT),使之能跟踪亚象素的位移,发现GLUT4在胞内虽然有两个循环路径,但是在无刺激的情况下,它的运动呈现限制性运动,其分散系数呈现一种连续的平滑的分布,即其运动并未因循环有两个路径而分成几种形式。
此外,我们初步研究了囊泡转运与细胞膜脂筏的关系。首先构建了含荧光标记
The vesicles transport is a complicated system in cell in which materials are transfered any abnormity of the system would results in corresponding deseases. Vesicles function as transport carries and can be regulated. Lipid-Raft is a microdomain containing special lipids and proteins between the two layers of cell membranes and plays an important role in vesicles transport. In this thesis, single melecular technique and total internal reflex fluorecence microscope imaging technique were used to investigate the location and mobility characteristics of Glucose Transporter 4 in the real-time dynamic and space location relation between the large dense core vesicles (LDCVs) and two kinds of lipid raft.The study will be very interesting in illustrations of the mechenisms of vesicles transport as well as of diabetes and helpneses in developing the drugs targeting at GLUT4 and benifical in further sighting into the functions of lipid-raft.
It is an importance of homeostasis body’s glucose. It is known that insulin is important hormone to regulate balance of blood glucose. Insulin helps to transport glucose cross plasma membrane into cells and decrease glucose level in blood. In fact, the effect of insulin is dependent on the effect of GLUT4 in some degree. Therefore, the GLUT4 becomes a key factor of regulation in balance of blood glucose. Evidences show the type2 diabetes is related with the abnormity of transportation of GLUT4. The transport of GLUT4 is regulated by many factors, which include its sequestration mechanism in cells, dynamic sorting, assemble secretory vesicles and structure of membrane lipid. GLUT4 transportation in cells has two recycling pathways. The cycle 1 occurs between the cell surface and endosomes and cycle 2 between the trans-Golgi network (TGN) and endosomes. It seems likely that various recycling loops must be coordinated in regulating the trafficking of intracellular GLUT4. Although different GLUT4 trafficking pathways have been proposed, it is still unclear whether GLUT4 is classified into distinct patterns according to their mobility. It would be clearly helpful to
investigate the mobility of a single GLUT4 in living cells. Here we have labeled the GLUT4 by constructing a fusion protein linking EGFP to the C-terminus of mouse GLUT4. The GLUT4-EGFP fusion protein was expressed in 3T3-L1 cells by transient transfection. By using total internal reflection fluorescence microscopy (TIRFM), the corresponding fluorescence images of GLUT4-EGFP fusion protein were recorded in charge coupled device (CCD) at high time resolution. In order to obtain the sub-pixel displacement of GLUT4, we employed a Gaussian-based single particle tracking (SPT) method to resolve the kinetics of vesicle motion. We found that GLUT4 moves in a constrained fashion as if it is tethered by some intracellular structure. The distribution of the three-dimensional diffusion coefficients (D(3)) was a smooth continuum. Our results demonstrate that even the existence of different recycling loops for GLUT4, they still are organized in a continuous range of mobility rather than into separated classes in intact 3T3-L1, but they are organized in two kinds of mobility pools after stimulation by insulin. In addition, we have studied the relationships between the vesicles transport and lipid rafts. Lipid rafts are specific membrane microdomains that are rich in cholesterol, glycosphingolipids and glycosylphosphatidylinositol linked molecules. They play role in the system of protein trafficking. Here we have labeled the Caveolin and flotillin, which are two kinds of marker proteins of rafts by constructing a fusion protein that links EGFP, and labeled the NPY and SNAP25 by constructing a fusion protein that links DsRed. The fusion proteins were expressed in PC12 cells by transient transfection. By using total internal reflection fluorescence microscopy (TIRFM), the corresponding fluorescence images were recorded with charge coupled device (CCD) at high time resolution. We found that Caveolin is not in colocation with NPY during free-stimulation and stimulation with high concentration K+, and neither colocation with SNAP25. Flotillin does not distinctly coexisted with NPY. The results show that rafts may not take part in the transport procedure of LDCVs with NPY. The results are not consistent with that from biochemical approaches. The difference may be interpreted by two ways: on the one hand,
it is possibility that rafts take part in small vesicles transport but no do in LDCVs, because the two kinds of vesicles have actually different mechanism of transport; on the other hand different results attribute to different experimental ways. It is very necessary that we must develop new methods to study rafts.
机体内葡萄糖的平衡对生命过程至关重要。胰岛素是调节血糖平衡的重要激素,它促进葡萄糖进入细胞内,从而降低血中葡萄糖。胰岛素的这一作用是通过细胞内的葡萄糖转运体(Glucose Transporter,GLUT)家族之一葡萄糖转运子4(GLUT4)将葡萄糖从细胞外转运到细胞内的。研究表明II型糖尿病的发生与细胞内GLUT4的转运障碍有关。而GLUT4的转运被认为是受多种因素控制的,这些因素目前较公认的有GLUT4在细胞器中的保持机制、动态分选、囊泡的转运、锚定和与质膜的融合以及质膜的脂质结构。GLUT4在细胞内的转运至少有两个循环,一个是细胞表面和内涵体间的循环,一个是在trans-Golgi network (TGN) 和内涵体间的循环。在这两个循环中GLUT4转位有几个严格的控制点。这两个循环似乎告诉我们GLUT4在胞内可能有两种运动形式。为了回答这个问题,我们研究了GLUT4在胞内的动力学过程。在研究过程中使用Confocal显微镜观察了GLUT4在胞内的整体分布。使用全内反射荧光显微镜时序成像获得了GLUT4的动态连续的图像,用于三维动力学分析。分析中发展了单颗粒追踪方法(SPT),使之能跟踪亚象素的位移,发现GLUT4在胞内虽然有两个循环路径,但是在无刺激的情况下,它的运动呈现限制性运动,其分散系数呈现一种连续的平滑的分布,即其运动并未因循环有两个路径而分成几种形式。
此外,我们初步研究了囊泡转运与细胞膜脂筏的关系。首先构建了含荧光标记
The vesicles transport is a complicated system in cell in which materials are transfered any abnormity of the system would results in corresponding deseases. Vesicles function as transport carries and can be regulated. Lipid-Raft is a microdomain containing special lipids and proteins between the two layers of cell membranes and plays an important role in vesicles transport. In this thesis, single melecular technique and total internal reflex fluorecence microscope imaging technique were used to investigate the location and mobility characteristics of Glucose Transporter 4 in the real-time dynamic and space location relation between the large dense core vesicles (LDCVs) and two kinds of lipid raft.The study will be very interesting in illustrations of the mechenisms of vesicles transport as well as of diabetes and helpneses in developing the drugs targeting at GLUT4 and benifical in further sighting into the functions of lipid-raft.
It is an importance of homeostasis body’s glucose. It is known that insulin is important hormone to regulate balance of blood glucose. Insulin helps to transport glucose cross plasma membrane into cells and decrease glucose level in blood. In fact, the effect of insulin is dependent on the effect of GLUT4 in some degree. Therefore, the GLUT4 becomes a key factor of regulation in balance of blood glucose. Evidences show the type2 diabetes is related with the abnormity of transportation of GLUT4. The transport of GLUT4 is regulated by many factors, which include its sequestration mechanism in cells, dynamic sorting, assemble secretory vesicles and structure of membrane lipid. GLUT4 transportation in cells has two recycling pathways. The cycle 1 occurs between the cell surface and endosomes and cycle 2 between the trans-Golgi network (TGN) and endosomes. It seems likely that various recycling loops must be coordinated in regulating the trafficking of intracellular GLUT4. Although different GLUT4 trafficking pathways have been proposed, it is still unclear whether GLUT4 is classified into distinct patterns according to their mobility. It would be clearly helpful to
investigate the mobility of a single GLUT4 in living cells. Here we have labeled the GLUT4 by constructing a fusion protein linking EGFP to the C-terminus of mouse GLUT4. The GLUT4-EGFP fusion protein was expressed in 3T3-L1 cells by transient transfection. By using total internal reflection fluorescence microscopy (TIRFM), the corresponding fluorescence images of GLUT4-EGFP fusion protein were recorded in charge coupled device (CCD) at high time resolution. In order to obtain the sub-pixel displacement of GLUT4, we employed a Gaussian-based single particle tracking (SPT) method to resolve the kinetics of vesicle motion. We found that GLUT4 moves in a constrained fashion as if it is tethered by some intracellular structure. The distribution of the three-dimensional diffusion coefficients (D(3)) was a smooth continuum. Our results demonstrate that even the existence of different recycling loops for GLUT4, they still are organized in a continuous range of mobility rather than into separated classes in intact 3T3-L1, but they are organized in two kinds of mobility pools after stimulation by insulin. In addition, we have studied the relationships between the vesicles transport and lipid rafts. Lipid rafts are specific membrane microdomains that are rich in cholesterol, glycosphingolipids and glycosylphosphatidylinositol linked molecules. They play role in the system of protein trafficking. Here we have labeled the Caveolin and flotillin, which are two kinds of marker proteins of rafts by constructing a fusion protein that links EGFP, and labeled the NPY and SNAP25 by constructing a fusion protein that links DsRed. The fusion proteins were expressed in PC12 cells by transient transfection. By using total internal reflection fluorescence microscopy (TIRFM), the corresponding fluorescence images were recorded with charge coupled device (CCD) at high time resolution. We found that Caveolin is not in colocation with NPY during free-stimulation and stimulation with high concentration K+, and neither colocation with SNAP25. Flotillin does not distinctly coexisted with NPY. The results show that rafts may not take part in the transport procedure of LDCVs with NPY. The results are not consistent with that from biochemical approaches. The difference may be interpreted by two ways: on the one hand,
it is possibility that rafts take part in small vesicles transport but no do in LDCVs, because the two kinds of vesicles have actually different mechanism of transport; on the other hand different results attribute to different experimental ways. It is very necessary that we must develop new methods to study rafts.
引文
[1] Medina RA, Owen GI. Glucose transporters: expression, regulation and cancer. Biol Res, 2002, 35(1): 9-26
[2] Joost HG, Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members. Mol Membr Biol, 2001 Oct-Dec, 18(4): 247-56
[3] Michael P. Czech and Silvia Corvera Signaling Mechanisms That Regulate Glucose Transport. Biol. Chem, Jan 1999, 274(4): 1865-1868
[4] Doege H, Bocianski A, Joost HG, Schurmann A. Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes. Biochem J., 2000 Sep 15, 350 Pt 3: 771-6
[5] Kanai, F., Nishioka, Y. , Hayashi, H. , et. al Direct demonstration of insulin induced GLUT4 translocation to the surface of intact cells by insertion of a c-myc epitope into an exofacial GLUT4 domain. J Boil Chem, 1993, 268: 14523-14526
[6] Cairns, M. T., Alvarez, J. , Panico, M. , et. al. Investigation of the structure and fuction of the human erythrocyte glucose transporter by proteolytic dissection. Biochem Biophys Acta, 1987, 905: 295-310
[7] E. Wadzinski, F. Shanahan, B. Seamon. et. al. Location of the forskolin photolabelling site within the monosaccaride transporter human erythrocytes. Biochem J., 1990, 272: 151-158
[8] G. Joost, B. Thorrens The extended GLUT-family of sugar/polyol transport facilitators—Nomenclature, sequence characteristics, and potential function of its novel members. Mol Membr Biol, 2001, 18: 247-256
[9] P. Barrett, R. Walmsley, W. Gould Structure and function of facilitative sugar transporters. Curr Opin Cell Biol, 1999, 11: 496-502
[10] Haney PM, Slot JW, Piper RC, et. al. Intracllular targeting od the insulin regulatable glucose transporter 4 is isoform spcific and independent of cell type. J Cell Bio, 1991, 114: 689
[11] Piper RC, Tai C, Kulesza P, Pang S et. al. GLUT4 N-terminal contains a phenylalanine based targeting motif that regulates intracellular sequestration. J Cell Biol, 1993, 121: 1221
[12] Asano T, Takata K, Katagin H, et. al. Domains responsible for the differential targeting of glucose transporter isoforms. J Biol Chem, 1992, 267: 19636
[13] Verhey KJ, Hausdorff SF Birnbaum MJ. Identification of the carboxy terminus as important for the isoform specific subcellular targeting of glucose transporter protein. J Cell Biol, 1993, 123: 137
[14] Caech MP Buoccon JM. Insulin action on the internalization of the GLUT4 glucose transporter in isolated rat adipocytes. J Biol Chem, 1993, 268: 9187
[15] Marshell BA, Murata H, Hresko RC, et. Al. Domains that confer intracellular sequestration of the GLUT4 glucose transporter in Xeno-pus oocytes, J Biol Chem, 1993, 268: 26193
[16] Watson RT, Khan AH, Furukawa M, Hou JC, Li L, Kanzaki M, Okada S, Kandror KV, Pessin JE. Entry of newly synthesized GLUT4 into the insulin-responsive storage compartment is GGA dependent. EMBO J., 2004 May 19, 23(10): 2059-70, Epub. 2004 Apr 29
[17] Khan AH, Capilla E, Hou JC, Watson RT, Smith JR, Pessin JE. Entry of Newly Synthesized GLUT4 into the Insulin-responsive Storage Compartment Is Dependent upon Both the Amino Terminus and the Large Cytoplasmic Loop. J Biol Chem, 2004 Sep 3, 279(36): 37505-11
[18] Cantrell DA. Phosphoinositide 3-kinase signalling pathways. J Cell Sci., 2001 Apr, 114(Pt 8): 1439-45
[19] Gautam Bandyopadhyay, Mini P. Sajan, Yoshinori Kanoh et al. Glucose Activates Protein Kinase C-/ through Proline-rich Tyrosine Kinase-2, Extracellular Signal-regulated Kinase, and Phospholipase D. A novel mechanism for activating glucose transporter translocation. J. Biol. Chem, Sep 2001, 276: 35537-35545
[20] A. H. Khan, J. E. Pessin. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways Diabetologia, 2002, 45: 1475–1483
[21] Cormont M, Le Marchand-Brustel Y. The role of small G-proteins in the regulation of glucose transport (review). Mol Membr Biol, 2001 Jul-Sep, 18(3): 213-20
[22] Litherland GJ, Hajduch E, Hundal HS. Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues Mol Membr Biol, 2001 Jul-Sep, 18(3): 195-204
[23] Prasenjit Mitra, Xuexiu Zheng, and Michael P. Czech RNAi-based Analysis of CAP, Cbl, and CrkII Function in the Regulation of GLUT4 by Insulin. J Biol Chem, 2004 Sep 3, 279(36): 37431-5
[24] Summers SA, Whiteman EL, Cho H, Lipfert L, Birnbaum MJ. Differentiation-dependent suppression of platelet-derived growth factor signaling in cultured adipocytes. J Biol Chem, 1999, 274: 23858–23867
[25] Katagiri H, Asano T, Ishihara H et al. Overexpression of catalytic subunit p110 o?f phosphatidylinositol 3-kinase increases glucose transport activity with translocation of glucose transporters in 3T3-L1 adipocytes. J Biol Chem, 1996, 271: 16987–16990
[26] Slot JW, Geuze HJ, Gigengack S, Lienhard GE, James DE 17. Frevert EU, Kahn BB. Differential effects of constitutively active phosphatidylinositol 3-kinase on glucose transport, glycogen synthase activity, and DNA synthesis in 3T3-L1 adipocytes. Mol Cell Biol, 1997, 17: 190–198
[27] Jiang T, Sweeney G, Rudolf MT et al. Membranepermeant esters of phosphatidylinositol 3, 4, 5-trisphosphate. J Biol Chem, 1998, 273: 11017–11024
[28] Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel AR. A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes. Mol Cell Biol, 1998, 18: 872–879
[29] Moodie SA, Alleman-Sposeto J, Gustafson TA. Identification of the APS protein as a novel insulin receptor substrate. J Biol Chem, 1999, 274: 11186–11193
[30] Baumann CA, Ribon V, Kanzaki M et al. CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature, 2000, 407: 202–207
[31] Chiang SH, Baumann CA, Kanzaki M et al. Insulinstimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature, 2001, 410: 944–948
[32] Neudauer CL, Joberty G, Tatsis N, Macara IG. Distinct cellular effects and interactions of the Rho-family GTPase TC10. Curr Biol, 1998, 8: 1151–1160
[33] Bickel PE, Scherer PE, Schnitzer JE et al. Flotillin and epidermal surface antigen define a new family of Caveolae-associated integral membrane proteins. J Biol Chem, 1997, 272: 13793–13802
[34] Kimura A, Baumann CA, Chiang SH, Saltiel AR. The sorbin homology domain: a motif for the targeting of proteins to lipid rafts. Proc Natl Acad Sci USA 98, 2001: 9098–9103
[35] Gotoh T, Hattori S, Nakamura S et al. Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol Cell Biol, 1995, 15: 6746–6753
[36] Tomas E, Zorzano A, Ruderman NB. Exercise and insulin signaling: a historical perspective. J Appl Physiol, 2002 Aug, 93(2): 765-72
[37] Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med, 1998, 49: 235-61
[38] Etgen GJ Jr, Fryburg DA, Gibbs EM. Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction-and phosphatidylinositol-3-kinase-independent pathway. Diabetes, 1997, 46(11): 1915-9
[39] Young ME, Radda GK, Leighton B. Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro. Biochem J., 1997 Feb 15, 322 ( Pt 1): 223-228
[40] Kapur S, Bedard S, Marcotte B, Cote CH, Marette A. Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action. Diabetes, 1997 Nov, 46(11): 1691-1700
[41] Han XX, Bonen A. Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle. Am J Physiol, 1998 Apr, 274(4 Pt 1): E700-704
[42] Shimizu, Y., Kielar, D., Minokoshi, Y., and Shimazu, T. Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin. Biochem J., 1996 Mar 1, 314 ( Pt 2): 485-90
[43] Fischer, Y., Kamp, J., Thomas, J., Popping, S., Rose, H., Carpene, C., and Kammermeier, H. Signals mediating stimulation of cardiomyocyte glucose transport by the alpha-adrenergic agonist phenylephrine. Am. J. Physiol, 1996, 270: C1211–C1220
[44] Kishi, K., Muromoto, N., Kakaya, Y. , Miyata, I. , Hagi, A. , Hayashi, H. , and Ebina, Y. Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. Diabetes, 1998 Apr, 47(4): 550-8
[45] Hansen, P. A., Corbett, J. A., and Holloszy, J. O. Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathways. Am J Physiol, 1997 Jul, 273(1 Pt 1): E28-36
[46] Omatsu-Kambe, M., Zarnowski, M. J. , and Cushman, S. W. Hormonal regulation of glucose transport in a brown adipose cell preparation isolated from rats that shows a large response to insulin. Biochem J., 1996 Apr 1, 315 ( Pt 1): 25-31
[47] Czech MP, Corvera S. Signaling mechanisms that regulate glucose transport. J Biol Chem, 1999 Jan 22, 274(4): 1865-8
[48] Dong Chen, Jeffrey S. Elmendorf, Ann Louise Olson, Xiong Li, H. Shelton Earp, and Jeffrey E. Pessin. Osmotic Shock Stimulates GLUT4 Translocation in 3T3L1 Adipocytes by a Novel Tyrosine Kinase Pathway J. Biol. Chem., Oct 1997, 272(43): 27401-27410
[49] Jeffrey S. Elmendorf, Dong Chen, and Jeffrey E. Pessin. Guanosine 5'-O-(3-Thiotriphosphate) (GTP S) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent J. Biol. Chem, May 1998, 273(21): 13289–13296
[50] Sajan M. P., Bandyopadhyay, G. , Kanoh, Y. , Standaert, M. L. , Quon, M. J. , Reed, B. C. , Dikic, I. , Farese, R. V. Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D. Biochem J., 2002 Mar 15, 362(Pt 3): 665-74
[51] Grusovin J, Macaulay SL. Snares for GLUT4 mechanisms directing vesicular trafficking of GLUT4 Front Biosci, 2003 May 1, 8: d 620-41
[52] Spurlin BA, Park SY, Nevins AK, Kim JK, Thurmond DC. Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. Diabetes, 2004 Sep, 53(9): 2223-31
[53] Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M. J Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2 Biol Chem, 2000 Mar 17, 275(11): 8240-7
[54] Khan, A. H., et al. 2001. Munc18c regulates insulin-stimulated GLUT4 translocation to the transverse tubules in skeletal muscle. J. Biol., Chem 276: 4063–4069
[55] L. Foster, A. Klip. Mechanism and regulation of GLUT4 vesicle fusion in muscles and fat cells. Am J Physiol, 2000, 279: C877-890
[56] Maxfield F R. Plasma membrane microdomains. Curr Opin CellBiol, 2002, 14(4): 483-487
[57] 杨福愉. 生物膜结构研究的一些进展. 生物化学与生物物理进展, 2003, 30(4): 495-502
[58] Simons K, Ikonen E. Functional rafts in cell membranes. Nature, 1997, 387: 569-572
[59] 陈岚, 许彩民, 袁建刚, 潘华珍. 脂筏的结构与功能. 生物化学与生物物理进展, 2003, 30(1): 54-59
[60] Perry E. Bickel. Lipid rafts and insulin signaling. Am J Physiol Endocrinol Metab, 2002, 282: E1-E10
[61] Sean Munro. Lipid Rafts: Elusive or Illusive. Cell, 2003, 115(11): 377-388
[62] Eric C. Lai. Lipid rafts make for slippery platforms. The Journal of Cell Biology, 2003, 162(8): 365-370
[63] Santos Manes, Gustavo del Real and Carlos Martinez-A. Pathogens: Raft Hijackers. Nature Review immunology, 2003, 3(7): 557-568
[64] Elina Ikonen. Roles of lipid rafts in membrane transport. Current Opinion in Cell Biology, 2001, 13: 470-477
[65] John P Incardona and Suzanne Eaton. Cholesterol in signal transduction. Current Opinion in Cell Biology, 2000, 12: 193–203
[65] Sanna Heino, Sari Lusa, Pentti Somerharju, Christian Ehnholm, Vesa M. Olkkonen, and Elina Ikonen. Dissecting the role of the Golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface. Proc. Natl. Acad. Sci. U. S. A. 2000, 97: 8375-8380
[66] P. Keller, K. Simons. Post-Golgi biosynthetic trafficking. J. Cell Sci. 1997,110: 3001-3009
[67] Anderson R G W. The Caveolae membrane system. Ann Rev Biochen, 1998, 67: 199-225
[68] Razani B, Schlegel A, Lisanti MP. Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. J Cell Sci, 2000, 113(12): 2103-2109
[69] Song KS, Scherer PE, Tang Z, et al. Expression of Caveolin2-3 in skeletal, cardiac, and smooth muscle cells. Caveolin23 is a component of the sarcolemma and co2fractionates with dystrophin and dystrophin2associated glycoproteins. J Biol Chem, 1996, 271(25): 15160-15165
[70] Tang Z, Scherer PE, Okamoto T, et al. Molecular cloning of Caveolin2 3, a novel member of the Caveolin gene family expressed predominantly in muscle. J Biol Chem, 1996, 271(4): 2255-2261
[71] Scherer PE, Lewis RY, Volonte D, et al. Cell type and tissue specific expression of Caveolin-2. Caveolins-1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. J Biol Chem, 1997, 272(46): 29337 -29346
[72] Li S, Song KS, Lisanti MP. Expression and characterization of recombinant Caveolin. Purification by polyhistidine tagging and cholesterol dependent incorporation into defined lipid membranes. J Biol Chem, 1996, 271 (1): 568-573
[73] Li S, Okamoto T, Chun M, et. al. Evidence for a regulated interaction between heterotrimeric Gproteins and Caveolin. J Biol Chem, 1995, 270(26): 15693 -15701
[74] Song KS, Li S, Okamoto T, et al. Expression of Caveolin23 in skeletal, cardiac, and smooth muscle cells. Caveolin23 is a component of the sarcolemma and co2fractionates with dystrophin and dystrophin2associated glycoproteins. J Biol Chem, 1996, 271(16): 9690-9697
[75] Li S, Couet J, Lisanti MP. Src tyrosine kinases, Galpha subunits, and H2Ras share a common membrane2anchored scaffolding protein, Caveolin. Caveolin binding negatively regulates the au0to2activation of Src tyrosine kinases. J Biol Chem, 1996, 271(46): 29182 -29190
[76] Feron O, Saldana F, Michel JB, et al. The endothelial nitric2oxide synthase Caveolin regulatory cycle. J Biol Chem, 1998, 273(6): 3125-3128
[77] Couet J, Sargiacomo M, Lisanti MP. Interaction of a receptor tyrosine kinase, EGF2R, with Caveolins. Caveolin binding negatively regulates tyrosine and serine/ threonine kinase activities . J Biol Chem, 1997, 272(48): 30429-30438
[78] Rybin VO, Xu X, Steinberg SF. Activated protein kinase C isoforms target to cardiomyocyte Caveolae: stimulation of local protein phosphorylation. Circ Res, 1999, 84: 980-988
[79] Yamamoto M, Toya Y, Schwencke C, et al. Caveolin is an activator of insulin receptor signaling . J Biol Chem, 1998, 273(41): 26962 -26968
[80] Okamoto T, Schlegel A, Scherer PE, et al. Caveolins, a family of scaffolding proteins for organizing. Preassembled signaling complexes at the plasma membrane. J Biol Chem, 1998, 273(10): 5419-5422
[81] Iwanishi M, Haruta T, Takata Y, et al. A mutation ( Trp1193-Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance [J]. Diabetologia, 1993, 36: 414-422
[82] Salzer U, Hinterdorfer P, Hunger U, et al. Ca2+ dependent vesicle release from erythrocytes involves stomatin specific lipid rafts, synexin (annexin Ⅶ), and sorcin. Blood, 2002, 97(7): 2569-2577
[83] Martin Belmonte F, Puertollano R, Millan J, et al. The MAL proteolipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial Madin2Darby canine kidney and fischer rat thyroid cell lines. Mol Biol Cell, 2000, 11 (6): 2033-2045
[84] Brown D A, London E. Structure and function of sphingolipid and cholesterol rich membrane rafts. J Biol Chem, 2000, 275 (23): 17221-17224
[85] Galbiati F, Razani B, Lisanti M P. Emerging themes in lipid rafts and Caveolae. Cell, 2001, 106 (4): 403-411
[86] Tatsuo Suzuki. Lipid rafts at postsynaptic sites: distribution, function and linkage to postsynaptic density. Neuroscience Research, 2002, 44: 1-9
[87] Chamberlain, L. H. , Burgoyne, R. D. , and Gould, G. W. SNARE proteins are highly enriched in lipid rafts in PC12 cells: Implications for the spatial control of exocytosis. Proc. Natl. Acad. Sci. U. S. A, 2001, 98: 5619-5624
[88] Thorsten Lang, Dieter Bruns, Dirk Wenzel. et al. SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J, 2001, 20, 2202–2213
[89] Luke H. Chamberlain and Gwyn W. Gould. The Vesicle-and Target-SNARE Proteins That Mediate GLUT4 Vesicle Fusion Are Localized in Detergent-insoluble Lipid Rafts Present on Distinct Intracellular Membranes. J Biol Chem, 2002, 277(12): 49750–49754
[90] Wang Y, Thiele C, Huttner WB: Cholesterol is required for the formation of regulated and constitutive secretory vesicles from the trans-Golgi network. Traffic, 2000, 1: 952-962
[91] Blasquez M, Thiele C, Huttner WB, Docherty K, Shennan KI: Involvement of the membrane lipid bilayer in sorting prohormone convertase-2 into the regulated secretory pathway. Biochemistry J., 2000, 349: 843-852
[92] Dhanvantari S, Loh YP: Lipid raft association of carboxypeptidase E is necessary for its function as a regulated secretory pathway sorting receptor. J Biol Chem, 2000, 275: 29887-29893
[93] Martin-Belmonte F, Alonso MA, Zhang X, Arvan P. Thyroglobulin is selected as luminal protein cargo for apical transport via detergent-resistant membranes in epithelial cells. J Biol Chem, 2000, 275: 41074-41081
[94] Schmidt K, Schrader M, Kern HF, Kleene R. Regulated apical. s?ecretion of zymogens in rat pancreas: involvement of the GPIanchored glycoprotein GP-2, the lectin ZG16p and cholesterolsphingolipid enriched microdomains. J Biol Chem, 2001, 276: 14315-14323
[95] Holowka D, Sheets ED, Baird B. Interactions between Fc(epsilon)RI and lipid raft components are regulated by the actin cytoskeleton. J Cell Sci, 2000, 113: 1009-1019
[96] Babiychuk EB, Draeger A. Annexins in cell membrane dynamicsC?a2+-regulated association of lipid microdomains. J Cell Biol, 2000, 150: 1113-1123
[97] Rozelle AL, Machesky LM, Yamamoto M, Driessens MHE, Insall RH, R?oth MG, Luby-Phelps K, Marriott G, Hall A, Yin HL: Phosphatidylinositol 4, 5-bisphosphate onduces actin-based movement of raft-enriched vesicles through WASP-Arp2/3. Curr Biol, 2000, 10: 311-320
[98] Nia J. Bryant, Roland Govers and David E. James. Regulated transport of the glucose transporter GLUT4. Nature Review/Molecular Cell Biology, 2002, 3(4): 267-277
[99] Roy S., Luetterforst R, Harding A, et al. Dominant-negative Caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains. Nature Cell Biol, 1999, 1(2): 98-105
[100] Karylowski O, Zeigerer A, Cohen A, McGraw TE. GLUT4 Is Retained by an Intracellular Cycle of Vesicle Formation and Fusion with Endosomes. Mol Biol Cell, 2004 Feb, 15(2): 870-82
[101] Tengholm, A. , Teruel, M. , and Meyer, T. Single cell imaging of PI3K activity and glucose transporter insertion into the plasma membrane by dual color evanescent wave microscopy. Sci. STKE 2003,169: 4
[102] Barrett, P., Bell, B., Cobelli, C., Golde, H., Schumitzky, A., Vicini, P. and Foster, D. SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism, 1998, 47: 484-492
[103] Cobelli, C., and Foster, D. Compartmental models: theory and practice using the SAAM II software system. Adv. Exp. Med. Biol, 1998, 445: 79-101
[104] Katz, E. B. et al. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature, 1995, 377: 151-155
[105] Tsao, T. S. et al. Muscle-specific transgenic complementation of GLUT4-deficient mice. Effects on glucose but not lipid metabolism. J. Clin. Invest, 1997, 100: 671-677
[106] Stenbit, A. E. et al. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat. Med. 3, 1997: 1096-1101
[107] Tsao, T. S. et al. Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle. Diabetes, 1999, 48: 775-782
[108] Zisman, A. et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat. Med. 6, 2000: 924-928
[109] Rodnick KJ, Slot JW, Studelska DR et al. Immunocytochemical and biochemical studies of GLUT4 in rat skeletal muscle. JBC, 1992, 267: 6278 6285
[110] Kahn BB, Charron MJ, Lodish HF, et al. Differential regulation of two glucose transporters in adipose cells from diabetic and insulin diabetic rats. J Clin Invest, 1989, 84: 404
[111] Frevert EU, Hamann A, Lowell BB et al. Decreased insulin action precedes down regulation of GLUT4 in adipocytes in a novel transgenic model of obesity and NIDDM. Diabetes, 1995, 44: 38-45
[112] Kahan BB, Pederson O. Suppression of GLUT4 expression in skeletal muscle of rats which are obese from high fat feeding but not from high carbohydrate feeding orgenetic obesity. Endocrinology, 1993, 132: 13-22
[113] Rosenblatt-Velin N, Lerch R, Papageorgiou I, Montessuit C. Insulin resistance in adult cardiomyocytes undergoing dedifferentiation: role of GLUT4 expression and translocation. FASEB J., 2004 May, 18(7): 872-4
[114] Mike Mueckler. Insulin resistance and the disruption of GLUT4 trafficking in skeletal muscle J Clin Invest, May 2001, 107(10): 1211-1213
[115] Wallberg-Henriksson H, Zierath JR. GLUT4: a key player regulating glucose homeostasis? Insights from transgenic and knockout mice. Mol Membr Biol, 2001 Jul-Sep, 18(3): 205-11
[116] Chalfie M., Tu Y. , Euskirchen G, Ward W W, et al. Green fluorescentprotein as a marker for gene expression. Science, 1994, 263: 802-805
[117] Prasher D. C. , et al. Primary structure of the Aequorea victoria green fluorescent protein. Gene, 1992, 111: 229-233
[118] Chalfie M., et al. Green fluorescent protein as a marker for gene expression. Science, 1994, 263: 802-805
[119] Inouye S. & Tsuji F. I. Aequorea green fluorescent protein: Expression of the gene and fluorescent characteristics of the recombinant protein. FEBS Letters, 1994, 341: 277-280
[120] Cormack B. et al. FACS-optimized mutants of the green fluorescent protein (GFP). Gene, 1996, 173: 33-38
[121] Haas J., et al. Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr Biol, 1996, 6: 315-324
[122] Matz M. V. , et al. Fluorescent proteins from nonbioluminescent Anthozoa species. Nature Biotech, 1999, 17: 969–973
[123] Gicquiaux H., Lecat S. , Gaire M. , et al. Rapid Internalization and Recycling of the Human Neuropeptide Y Y1 Receptor. J Biol Chem, 2002, 277: 6645 -6655
[124] Zunkler B. J. , Kuhne S. , Rustenbeck I. , et al. Mechanism of terfenadine block of ATP-sensitive K(+) channels. Br J Pharmacol, 2000, 130(7): 1571-4
[125] Lang T., Wacker I., Steyer rgen J., et al. Ca2+-Triggered Peptide Secretion Neurotechniquein Single Cells Imaged with Green FluorescentProtein and Evanescent-Wave Microscopy. Neuron, 1997, 18: 857–863
[126] Takuma T., Arakawa T., Okayama M., et al. Trafficking of green fluorescent protein-tagged SNARE proteins in HSY cells. J Biochem (Tokyo), 2002, 132(5): 729-35
[127] Schneider N. , Weber I. , Faix J. , et al. A Lim protein involved in the progression of cytokinesis and regulation of the mitotic spindle. Cell Motil Cytoskeleton, 2003, 56(2): 130-9
[128] Stanasila L., Perez J. B., Vogel H., et al. Oligomerization of the alpha1a and alpha1b-adrenergic receptor subtypes: potential implications in receptor internalization. J Biol Chem, 2003, 278(41): 40239-40251
[129] Tokunaga M, Yanagida T. Single molecule imaging of fluorophores and enzymatic reactions achieved by objective-type total internal reflection fluorescence microscopy. Biochem Biophys Res Commun, 1997, 235: 47–53
[130] Yoshikazu Suzuki, Tomomi Tani, Kazuo Sutoh, Shinji Kamimura. Imaging of the fluorescence spectrum of a single fluorescent molecule by prism-based spectroscopy. FEBS Letters, 2002, 512: 235-239
[131] Li Ma, Vytautas P. Bindokas, Andrey Kuznetsov. et. al. Direct imaging shows that insulin granule exocytosis occurs by complete vesicle fusion. PNAS, 2004, 101(25): 9266–9271
[132] Thompson NL, Lagerholm BC. Total internal reflection fluorescence: applications in cellular biophysics. Curr Opin Biotechnol. 1997; 8(1): 58-64.
[133] Cheezum MK, Walker WF, Guilford WH. Quantitative comparison of algorithms for tracking single fluorescent particles. Biophys J, 2001, 81(10): 2378-2388
[134] Petersen KF, Shulman GI. Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. Am J Cardiol, 2002, 90(5A): 11G-18G.
[135] Hirohito Sone, Hiroaki Suzuki, Akimitsu Takahashi and Nobuhiro Yamada. Disease model: hyperinsulinemia and insulin resistance. TRENDS in Molecular Medicine, 2001,7(7): 320-322
[136] Garvey WT. Glucose transport and NIDDM. Diabetes Care, 1992, 15(3): 396-417
[137] Bogan JS, Hendon N, McKee AE, Tsao TS, Lodish HF. Functional cloning of TUG as a regulator of GLUT4 glucose transporter trafficking. Nature, 2003, 425(10): 727-734
[138] Lampson MA, Schmoranzer J, Zeigerer A, Simon SM, McGraw TE. Insulin-regulated Release from the Endosomal Recycling Compartment Is Regulated by Budding of Specialized Vesicles. Mol Biol Cell, 2001, 12(11): 3489-3501
[139] Zeigerer A, Lampson MA, Karylowski O, Sabatini DD, Adesnik M, Ren M, McGraw TE. GLUT4 retention in adipocytes requires two intracellular insulin-regulated transport steps. Mol Biol Cell, 2002, 13(7): 2421-2435
[140] Molloy SS, Anderson ED, Jean F, Thomas G. Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis. Trends Cell Biol, 1999, 9(1): 28–35
[141] Xaing Y, Molloy SS, Thomas L, Thomas G. The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments. Mol Biol Cell, 2000, 11(4): 1257-1273
[142] Martin S, Ramm G, Lyttle CT, Meerloo T, Stoorvogel W, James DE. Biogenesis of insulin-responsive GLUT4 vesicles is independent of brefeldin A-sensitive trafficking. Traffic, 2000, 1(8): 652-660
[143] Palacios S, Lalioti V, Martinez-Arca S, Chattopadhyay S, Sandoval IV. Recycling of the insulin-sensitive glucose transporter GLUT4. Access of surface internalized GLUT4 molecules to the perinuclear storage compartment is mediated by the Phe5-Gln6-Gln7-Ile8 motif. J Biol Chem, 2001, 276(5): 3371-3383
[144] Jahn R, Lang T, Südhof TC. Membrane Fusion. Cell, 2003, 112(2): 519–533
[145] Hashiramoto M, James DE. Characterization of insulin-responsive GLUT4 vesicles isolated from 3T3-L1 adipocytes. Mol Cell Biol, 2000, 20(1): 416-427
[146] Ramm G, Slot JW, James DE, Stoorvogel W. Insulin recruits GLUT4 from specialized VAMP2-carrying vesicles as well as from the dynamic endosomal/trans-Golgi network in rat adipocytes. Mol Biol Cell, 2000, 11(12): 4079-4091
[147] Kues T, Dickmanns A, Luhrmann R, Peters R, Kubitscheck U. High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP observed by single particle tracking. Proc Natl Acad Sci U S A, 2001, 98(21): 12021-12026
[148] Goulian M, Simon SM. Tracking single proteins within cells. Biophys J, 2000, 79(10): 2188-2198
[149] Thompson RE, Larson DR, Webb WW. Precise nanometer localization analysis for individual fluorescent probes. Biophys J, 2002, 82(5): 2775-2783
[150] Olveczky BP, Periasamy N, Verkman AS. Mapping fluorophore distributions in three dimensions by quantitative multiple angle-total internal reflection fluorescence microscopy. Biophys J, 1997, 73(5): 2836-2847
[151] Steyer JA, Almers W. A real-time view of life within 100 nm of the plasma membrane. Nat Rev Mol Cell Biol, 2001, 2(4): 268-275
[152] Oheim, M, Stühmer M. Tracking chromaffin granules on their way through the actin cortex. Eur Biophys J, 2000, 29(2): 67-89
[153] Rizzuto R, Carrington W, Tuft RA. Digital imaging microscopy of living cells. Trends Cell Biol, 1998, 8(7): 288-292
[154] Steyer JA, Almers W. Tracking single secretory granules in live chromaffin cells by evanescent-field fluorescence microscopy. Biophys J, 1999, 76(4): 2262-2271
[155] Becherer U, Moser T, Stuhmer W, Oheim M. Calcium regulates exocytosis at the level of single vesicles. Nat Neurosci, 2003, 6(8): 846-853
[156] Lang T, Wacker I, Wunderlich I, Rohrbach A, Giese G, Soldati T, Almers W. Role of actin cortex in the subplasmalemmal transport of secretory granules in PC-12 cells. Biophys J, 2000, 78(6): 2863-2877
[157] Qian H, Sheetz MP, Elson EL. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys J, 1991, 60(10): 910-921
[158] Saxton MJ, Jacobson K. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct, 1997, 26: 373-399
[159] Saxton MJ. Single-particle tracking: the distribution of diffusion coefficients. Biophys J, 1997, 72(4): 1744-1753
[160] Ng YK, Lu X, Gulacsi A, Han W, Saxton MJ, Levitan ES. Unexpected mobility variation among individual secretory vesicles produces an apparent refractory neuropeptide pool. Biophys J, 2003, 84(6): 4127 –4134
[161] Liu LB, Omata W, Kojima I, Shibata H. Insulin Recruits GLUT4 from Distinct Compartments via Distinct Traffic Pathways with Differential Microtubule Dependence in Rat Adipocytes. J Biol Chem, 2003, 278(32): 30157-30169
[162] Johns LM, Levitan ES, Shelden EA, Holz RW, Axelrod D. Restriction of secretory granule motion near the plasma membrane of chromaffin cells. J Cell Biol, 2001, 153(4): 177-190
[163] Hirokawa N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science, 1998, 279(5350): 519-526
[164] Kamal A, Goldstein LS. Principles of cargo attachment to cytoplasmic motor proteins. Curr Opin Cell Biol, 2002, 14(1): 63-68
[165] Thorn, N. A. In vitro studies of the release mechanism for vasopressin in rats. Acta Endocrinol, 1966, 53: 644–654
[166] Burke, N., W. Han, D. Li, K. Takimoto, S. C. Watkins, and E. S. Levitan. Neuronal peptide release is limited by secretory granule mobility. Neuron, 1997, 19: 1095–1102
[167] 周镜然. Caveolin家族分子研究进展. 细胞生物学杂志, 2002: 338-342
[168] Ulrich Salzar and Rainer Prohaska. Stomatin, flotillin-1 and flotillin-2 are major integral proteins of erythrocyte lipid rafts. BLOOD, 2001, 97(4): 1141-1143
[169] Mukherjee, S., Zha, X., Tabas, I., and Maxfield, F.R.. Choles-terol distribution in living cells: fluorescence imaging using dehydroergosteol as a fluorescent cholesterol analog. Biophys. J., 1998, 75: 1915–1925
[170] Mayor, S., Rothberg, K.G., and Maxfield, F.R.. Sequestration of GPI-anchored proteins in Caveolae triggered by cross-linking. Science, 1994, 264: 1948–1951
[171] Chen, C.S., Martin, O.C., and Pagano, R.E.. Changes in the spectral properties of a plasma membrane lipid analog during the first seconds of endocytosis in living cells. Biophys. J., 1997, 72: 37–50
[172] Kenworthy, A.K., Petranova, N., and Edidin, M. High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. Mol. Biol. Cell , 2000: 1645–1655
[173] Vrljic, M., Nishimura, S.Y., Brasselet, S., Moerner, W.E., and McConnell, H.M.. Translational diffusion of individual class II MHC membrane proteins in cells. Biophys. J., 2002, 83: 2681–2692
[174] Anderson, R.G., and Jacobson, K. A role for lipid shells in targeting proteins to Caveolae, rafts, and other lipid domains. Science, 2002, 296: 1821–1825
[175] Zacharias, D.A., Violin, J.D., Newton, A.C., and Tsien, R.Y.. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science, 2002, 296: 913–916
[2] Joost HG, Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members. Mol Membr Biol, 2001 Oct-Dec, 18(4): 247-56
[3] Michael P. Czech and Silvia Corvera Signaling Mechanisms That Regulate Glucose Transport. Biol. Chem, Jan 1999, 274(4): 1865-1868
[4] Doege H, Bocianski A, Joost HG, Schurmann A. Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes. Biochem J., 2000 Sep 15, 350 Pt 3: 771-6
[5] Kanai, F., Nishioka, Y. , Hayashi, H. , et. al Direct demonstration of insulin induced GLUT4 translocation to the surface of intact cells by insertion of a c-myc epitope into an exofacial GLUT4 domain. J Boil Chem, 1993, 268: 14523-14526
[6] Cairns, M. T., Alvarez, J. , Panico, M. , et. al. Investigation of the structure and fuction of the human erythrocyte glucose transporter by proteolytic dissection. Biochem Biophys Acta, 1987, 905: 295-310
[7] E. Wadzinski, F. Shanahan, B. Seamon. et. al. Location of the forskolin photolabelling site within the monosaccaride transporter human erythrocytes. Biochem J., 1990, 272: 151-158
[8] G. Joost, B. Thorrens The extended GLUT-family of sugar/polyol transport facilitators—Nomenclature, sequence characteristics, and potential function of its novel members. Mol Membr Biol, 2001, 18: 247-256
[9] P. Barrett, R. Walmsley, W. Gould Structure and function of facilitative sugar transporters. Curr Opin Cell Biol, 1999, 11: 496-502
[10] Haney PM, Slot JW, Piper RC, et. al. Intracllular targeting od the insulin regulatable glucose transporter 4 is isoform spcific and independent of cell type. J Cell Bio, 1991, 114: 689
[11] Piper RC, Tai C, Kulesza P, Pang S et. al. GLUT4 N-terminal contains a phenylalanine based targeting motif that regulates intracellular sequestration. J Cell Biol, 1993, 121: 1221
[12] Asano T, Takata K, Katagin H, et. al. Domains responsible for the differential targeting of glucose transporter isoforms. J Biol Chem, 1992, 267: 19636
[13] Verhey KJ, Hausdorff SF Birnbaum MJ. Identification of the carboxy terminus as important for the isoform specific subcellular targeting of glucose transporter protein. J Cell Biol, 1993, 123: 137
[14] Caech MP Buoccon JM. Insulin action on the internalization of the GLUT4 glucose transporter in isolated rat adipocytes. J Biol Chem, 1993, 268: 9187
[15] Marshell BA, Murata H, Hresko RC, et. Al. Domains that confer intracellular sequestration of the GLUT4 glucose transporter in Xeno-pus oocytes, J Biol Chem, 1993, 268: 26193
[16] Watson RT, Khan AH, Furukawa M, Hou JC, Li L, Kanzaki M, Okada S, Kandror KV, Pessin JE. Entry of newly synthesized GLUT4 into the insulin-responsive storage compartment is GGA dependent. EMBO J., 2004 May 19, 23(10): 2059-70, Epub. 2004 Apr 29
[17] Khan AH, Capilla E, Hou JC, Watson RT, Smith JR, Pessin JE. Entry of Newly Synthesized GLUT4 into the Insulin-responsive Storage Compartment Is Dependent upon Both the Amino Terminus and the Large Cytoplasmic Loop. J Biol Chem, 2004 Sep 3, 279(36): 37505-11
[18] Cantrell DA. Phosphoinositide 3-kinase signalling pathways. J Cell Sci., 2001 Apr, 114(Pt 8): 1439-45
[19] Gautam Bandyopadhyay, Mini P. Sajan, Yoshinori Kanoh et al. Glucose Activates Protein Kinase C-/ through Proline-rich Tyrosine Kinase-2, Extracellular Signal-regulated Kinase, and Phospholipase D. A novel mechanism for activating glucose transporter translocation. J. Biol. Chem, Sep 2001, 276: 35537-35545
[20] A. H. Khan, J. E. Pessin. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways Diabetologia, 2002, 45: 1475–1483
[21] Cormont M, Le Marchand-Brustel Y. The role of small G-proteins in the regulation of glucose transport (review). Mol Membr Biol, 2001 Jul-Sep, 18(3): 213-20
[22] Litherland GJ, Hajduch E, Hundal HS. Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues Mol Membr Biol, 2001 Jul-Sep, 18(3): 195-204
[23] Prasenjit Mitra, Xuexiu Zheng, and Michael P. Czech RNAi-based Analysis of CAP, Cbl, and CrkII Function in the Regulation of GLUT4 by Insulin. J Biol Chem, 2004 Sep 3, 279(36): 37431-5
[24] Summers SA, Whiteman EL, Cho H, Lipfert L, Birnbaum MJ. Differentiation-dependent suppression of platelet-derived growth factor signaling in cultured adipocytes. J Biol Chem, 1999, 274: 23858–23867
[25] Katagiri H, Asano T, Ishihara H et al. Overexpression of catalytic subunit p110 o?f phosphatidylinositol 3-kinase increases glucose transport activity with translocation of glucose transporters in 3T3-L1 adipocytes. J Biol Chem, 1996, 271: 16987–16990
[26] Slot JW, Geuze HJ, Gigengack S, Lienhard GE, James DE 17. Frevert EU, Kahn BB. Differential effects of constitutively active phosphatidylinositol 3-kinase on glucose transport, glycogen synthase activity, and DNA synthesis in 3T3-L1 adipocytes. Mol Cell Biol, 1997, 17: 190–198
[27] Jiang T, Sweeney G, Rudolf MT et al. Membranepermeant esters of phosphatidylinositol 3, 4, 5-trisphosphate. J Biol Chem, 1998, 273: 11017–11024
[28] Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel AR. A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes. Mol Cell Biol, 1998, 18: 872–879
[29] Moodie SA, Alleman-Sposeto J, Gustafson TA. Identification of the APS protein as a novel insulin receptor substrate. J Biol Chem, 1999, 274: 11186–11193
[30] Baumann CA, Ribon V, Kanzaki M et al. CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature, 2000, 407: 202–207
[31] Chiang SH, Baumann CA, Kanzaki M et al. Insulinstimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature, 2001, 410: 944–948
[32] Neudauer CL, Joberty G, Tatsis N, Macara IG. Distinct cellular effects and interactions of the Rho-family GTPase TC10. Curr Biol, 1998, 8: 1151–1160
[33] Bickel PE, Scherer PE, Schnitzer JE et al. Flotillin and epidermal surface antigen define a new family of Caveolae-associated integral membrane proteins. J Biol Chem, 1997, 272: 13793–13802
[34] Kimura A, Baumann CA, Chiang SH, Saltiel AR. The sorbin homology domain: a motif for the targeting of proteins to lipid rafts. Proc Natl Acad Sci USA 98, 2001: 9098–9103
[35] Gotoh T, Hattori S, Nakamura S et al. Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G. Mol Cell Biol, 1995, 15: 6746–6753
[36] Tomas E, Zorzano A, Ruderman NB. Exercise and insulin signaling: a historical perspective. J Appl Physiol, 2002 Aug, 93(2): 765-72
[37] Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med, 1998, 49: 235-61
[38] Etgen GJ Jr, Fryburg DA, Gibbs EM. Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction-and phosphatidylinositol-3-kinase-independent pathway. Diabetes, 1997, 46(11): 1915-9
[39] Young ME, Radda GK, Leighton B. Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro. Biochem J., 1997 Feb 15, 322 ( Pt 1): 223-228
[40] Kapur S, Bedard S, Marcotte B, Cote CH, Marette A. Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action. Diabetes, 1997 Nov, 46(11): 1691-1700
[41] Han XX, Bonen A. Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle. Am J Physiol, 1998 Apr, 274(4 Pt 1): E700-704
[42] Shimizu, Y., Kielar, D., Minokoshi, Y., and Shimazu, T. Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin. Biochem J., 1996 Mar 1, 314 ( Pt 2): 485-90
[43] Fischer, Y., Kamp, J., Thomas, J., Popping, S., Rose, H., Carpene, C., and Kammermeier, H. Signals mediating stimulation of cardiomyocyte glucose transport by the alpha-adrenergic agonist phenylephrine. Am. J. Physiol, 1996, 270: C1211–C1220
[44] Kishi, K., Muromoto, N., Kakaya, Y. , Miyata, I. , Hagi, A. , Hayashi, H. , and Ebina, Y. Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. Diabetes, 1998 Apr, 47(4): 550-8
[45] Hansen, P. A., Corbett, J. A., and Holloszy, J. O. Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathways. Am J Physiol, 1997 Jul, 273(1 Pt 1): E28-36
[46] Omatsu-Kambe, M., Zarnowski, M. J. , and Cushman, S. W. Hormonal regulation of glucose transport in a brown adipose cell preparation isolated from rats that shows a large response to insulin. Biochem J., 1996 Apr 1, 315 ( Pt 1): 25-31
[47] Czech MP, Corvera S. Signaling mechanisms that regulate glucose transport. J Biol Chem, 1999 Jan 22, 274(4): 1865-8
[48] Dong Chen, Jeffrey S. Elmendorf, Ann Louise Olson, Xiong Li, H. Shelton Earp, and Jeffrey E. Pessin. Osmotic Shock Stimulates GLUT4 Translocation in 3T3L1 Adipocytes by a Novel Tyrosine Kinase Pathway J. Biol. Chem., Oct 1997, 272(43): 27401-27410
[49] Jeffrey S. Elmendorf, Dong Chen, and Jeffrey E. Pessin. Guanosine 5'-O-(3-Thiotriphosphate) (GTP S) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent J. Biol. Chem, May 1998, 273(21): 13289–13296
[50] Sajan M. P., Bandyopadhyay, G. , Kanoh, Y. , Standaert, M. L. , Quon, M. J. , Reed, B. C. , Dikic, I. , Farese, R. V. Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D. Biochem J., 2002 Mar 15, 362(Pt 3): 665-74
[51] Grusovin J, Macaulay SL. Snares for GLUT4 mechanisms directing vesicular trafficking of GLUT4 Front Biosci, 2003 May 1, 8: d 620-41
[52] Spurlin BA, Park SY, Nevins AK, Kim JK, Thurmond DC. Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. Diabetes, 2004 Sep, 53(9): 2223-31
[53] Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M. J Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2 Biol Chem, 2000 Mar 17, 275(11): 8240-7
[54] Khan, A. H., et al. 2001. Munc18c regulates insulin-stimulated GLUT4 translocation to the transverse tubules in skeletal muscle. J. Biol., Chem 276: 4063–4069
[55] L. Foster, A. Klip. Mechanism and regulation of GLUT4 vesicle fusion in muscles and fat cells. Am J Physiol, 2000, 279: C877-890
[56] Maxfield F R. Plasma membrane microdomains. Curr Opin CellBiol, 2002, 14(4): 483-487
[57] 杨福愉. 生物膜结构研究的一些进展. 生物化学与生物物理进展, 2003, 30(4): 495-502
[58] Simons K, Ikonen E. Functional rafts in cell membranes. Nature, 1997, 387: 569-572
[59] 陈岚, 许彩民, 袁建刚, 潘华珍. 脂筏的结构与功能. 生物化学与生物物理进展, 2003, 30(1): 54-59
[60] Perry E. Bickel. Lipid rafts and insulin signaling. Am J Physiol Endocrinol Metab, 2002, 282: E1-E10
[61] Sean Munro. Lipid Rafts: Elusive or Illusive. Cell, 2003, 115(11): 377-388
[62] Eric C. Lai. Lipid rafts make for slippery platforms. The Journal of Cell Biology, 2003, 162(8): 365-370
[63] Santos Manes, Gustavo del Real and Carlos Martinez-A. Pathogens: Raft Hijackers. Nature Review immunology, 2003, 3(7): 557-568
[64] Elina Ikonen. Roles of lipid rafts in membrane transport. Current Opinion in Cell Biology, 2001, 13: 470-477
[65] John P Incardona and Suzanne Eaton. Cholesterol in signal transduction. Current Opinion in Cell Biology, 2000, 12: 193–203
[65] Sanna Heino, Sari Lusa, Pentti Somerharju, Christian Ehnholm, Vesa M. Olkkonen, and Elina Ikonen. Dissecting the role of the Golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface. Proc. Natl. Acad. Sci. U. S. A. 2000, 97: 8375-8380
[66] P. Keller, K. Simons. Post-Golgi biosynthetic trafficking. J. Cell Sci. 1997,110: 3001-3009
[67] Anderson R G W. The Caveolae membrane system. Ann Rev Biochen, 1998, 67: 199-225
[68] Razani B, Schlegel A, Lisanti MP. Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. J Cell Sci, 2000, 113(12): 2103-2109
[69] Song KS, Scherer PE, Tang Z, et al. Expression of Caveolin2-3 in skeletal, cardiac, and smooth muscle cells. Caveolin23 is a component of the sarcolemma and co2fractionates with dystrophin and dystrophin2associated glycoproteins. J Biol Chem, 1996, 271(25): 15160-15165
[70] Tang Z, Scherer PE, Okamoto T, et al. Molecular cloning of Caveolin2 3, a novel member of the Caveolin gene family expressed predominantly in muscle. J Biol Chem, 1996, 271(4): 2255-2261
[71] Scherer PE, Lewis RY, Volonte D, et al. Cell type and tissue specific expression of Caveolin-2. Caveolins-1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. J Biol Chem, 1997, 272(46): 29337 -29346
[72] Li S, Song KS, Lisanti MP. Expression and characterization of recombinant Caveolin. Purification by polyhistidine tagging and cholesterol dependent incorporation into defined lipid membranes. J Biol Chem, 1996, 271 (1): 568-573
[73] Li S, Okamoto T, Chun M, et. al. Evidence for a regulated interaction between heterotrimeric Gproteins and Caveolin. J Biol Chem, 1995, 270(26): 15693 -15701
[74] Song KS, Li S, Okamoto T, et al. Expression of Caveolin23 in skeletal, cardiac, and smooth muscle cells. Caveolin23 is a component of the sarcolemma and co2fractionates with dystrophin and dystrophin2associated glycoproteins. J Biol Chem, 1996, 271(16): 9690-9697
[75] Li S, Couet J, Lisanti MP. Src tyrosine kinases, Galpha subunits, and H2Ras share a common membrane2anchored scaffolding protein, Caveolin. Caveolin binding negatively regulates the au0to2activation of Src tyrosine kinases. J Biol Chem, 1996, 271(46): 29182 -29190
[76] Feron O, Saldana F, Michel JB, et al. The endothelial nitric2oxide synthase Caveolin regulatory cycle. J Biol Chem, 1998, 273(6): 3125-3128
[77] Couet J, Sargiacomo M, Lisanti MP. Interaction of a receptor tyrosine kinase, EGF2R, with Caveolins. Caveolin binding negatively regulates tyrosine and serine/ threonine kinase activities . J Biol Chem, 1997, 272(48): 30429-30438
[78] Rybin VO, Xu X, Steinberg SF. Activated protein kinase C isoforms target to cardiomyocyte Caveolae: stimulation of local protein phosphorylation. Circ Res, 1999, 84: 980-988
[79] Yamamoto M, Toya Y, Schwencke C, et al. Caveolin is an activator of insulin receptor signaling . J Biol Chem, 1998, 273(41): 26962 -26968
[80] Okamoto T, Schlegel A, Scherer PE, et al. Caveolins, a family of scaffolding proteins for organizing. Preassembled signaling complexes at the plasma membrane. J Biol Chem, 1998, 273(10): 5419-5422
[81] Iwanishi M, Haruta T, Takata Y, et al. A mutation ( Trp1193-Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance [J]. Diabetologia, 1993, 36: 414-422
[82] Salzer U, Hinterdorfer P, Hunger U, et al. Ca2+ dependent vesicle release from erythrocytes involves stomatin specific lipid rafts, synexin (annexin Ⅶ), and sorcin. Blood, 2002, 97(7): 2569-2577
[83] Martin Belmonte F, Puertollano R, Millan J, et al. The MAL proteolipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial Madin2Darby canine kidney and fischer rat thyroid cell lines. Mol Biol Cell, 2000, 11 (6): 2033-2045
[84] Brown D A, London E. Structure and function of sphingolipid and cholesterol rich membrane rafts. J Biol Chem, 2000, 275 (23): 17221-17224
[85] Galbiati F, Razani B, Lisanti M P. Emerging themes in lipid rafts and Caveolae. Cell, 2001, 106 (4): 403-411
[86] Tatsuo Suzuki. Lipid rafts at postsynaptic sites: distribution, function and linkage to postsynaptic density. Neuroscience Research, 2002, 44: 1-9
[87] Chamberlain, L. H. , Burgoyne, R. D. , and Gould, G. W. SNARE proteins are highly enriched in lipid rafts in PC12 cells: Implications for the spatial control of exocytosis. Proc. Natl. Acad. Sci. U. S. A, 2001, 98: 5619-5624
[88] Thorsten Lang, Dieter Bruns, Dirk Wenzel. et al. SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J, 2001, 20, 2202–2213
[89] Luke H. Chamberlain and Gwyn W. Gould. The Vesicle-and Target-SNARE Proteins That Mediate GLUT4 Vesicle Fusion Are Localized in Detergent-insoluble Lipid Rafts Present on Distinct Intracellular Membranes. J Biol Chem, 2002, 277(12): 49750–49754
[90] Wang Y, Thiele C, Huttner WB: Cholesterol is required for the formation of regulated and constitutive secretory vesicles from the trans-Golgi network. Traffic, 2000, 1: 952-962
[91] Blasquez M, Thiele C, Huttner WB, Docherty K, Shennan KI: Involvement of the membrane lipid bilayer in sorting prohormone convertase-2 into the regulated secretory pathway. Biochemistry J., 2000, 349: 843-852
[92] Dhanvantari S, Loh YP: Lipid raft association of carboxypeptidase E is necessary for its function as a regulated secretory pathway sorting receptor. J Biol Chem, 2000, 275: 29887-29893
[93] Martin-Belmonte F, Alonso MA, Zhang X, Arvan P. Thyroglobulin is selected as luminal protein cargo for apical transport via detergent-resistant membranes in epithelial cells. J Biol Chem, 2000, 275: 41074-41081
[94] Schmidt K, Schrader M, Kern HF, Kleene R. Regulated apical. s?ecretion of zymogens in rat pancreas: involvement of the GPIanchored glycoprotein GP-2, the lectin ZG16p and cholesterolsphingolipid enriched microdomains. J Biol Chem, 2001, 276: 14315-14323
[95] Holowka D, Sheets ED, Baird B. Interactions between Fc(epsilon)RI and lipid raft components are regulated by the actin cytoskeleton. J Cell Sci, 2000, 113: 1009-1019
[96] Babiychuk EB, Draeger A. Annexins in cell membrane dynamicsC?a2+-regulated association of lipid microdomains. J Cell Biol, 2000, 150: 1113-1123
[97] Rozelle AL, Machesky LM, Yamamoto M, Driessens MHE, Insall RH, R?oth MG, Luby-Phelps K, Marriott G, Hall A, Yin HL: Phosphatidylinositol 4, 5-bisphosphate onduces actin-based movement of raft-enriched vesicles through WASP-Arp2/3. Curr Biol, 2000, 10: 311-320
[98] Nia J. Bryant, Roland Govers and David E. James. Regulated transport of the glucose transporter GLUT4. Nature Review/Molecular Cell Biology, 2002, 3(4): 267-277
[99] Roy S., Luetterforst R, Harding A, et al. Dominant-negative Caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains. Nature Cell Biol, 1999, 1(2): 98-105
[100] Karylowski O, Zeigerer A, Cohen A, McGraw TE. GLUT4 Is Retained by an Intracellular Cycle of Vesicle Formation and Fusion with Endosomes. Mol Biol Cell, 2004 Feb, 15(2): 870-82
[101] Tengholm, A. , Teruel, M. , and Meyer, T. Single cell imaging of PI3K activity and glucose transporter insertion into the plasma membrane by dual color evanescent wave microscopy. Sci. STKE 2003,169: 4
[102] Barrett, P., Bell, B., Cobelli, C., Golde, H., Schumitzky, A., Vicini, P. and Foster, D. SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studies. Metabolism, 1998, 47: 484-492
[103] Cobelli, C., and Foster, D. Compartmental models: theory and practice using the SAAM II software system. Adv. Exp. Med. Biol, 1998, 445: 79-101
[104] Katz, E. B. et al. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature, 1995, 377: 151-155
[105] Tsao, T. S. et al. Muscle-specific transgenic complementation of GLUT4-deficient mice. Effects on glucose but not lipid metabolism. J. Clin. Invest, 1997, 100: 671-677
[106] Stenbit, A. E. et al. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat. Med. 3, 1997: 1096-1101
[107] Tsao, T. S. et al. Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle. Diabetes, 1999, 48: 775-782
[108] Zisman, A. et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat. Med. 6, 2000: 924-928
[109] Rodnick KJ, Slot JW, Studelska DR et al. Immunocytochemical and biochemical studies of GLUT4 in rat skeletal muscle. JBC, 1992, 267: 6278 6285
[110] Kahn BB, Charron MJ, Lodish HF, et al. Differential regulation of two glucose transporters in adipose cells from diabetic and insulin diabetic rats. J Clin Invest, 1989, 84: 404
[111] Frevert EU, Hamann A, Lowell BB et al. Decreased insulin action precedes down regulation of GLUT4 in adipocytes in a novel transgenic model of obesity and NIDDM. Diabetes, 1995, 44: 38-45
[112] Kahan BB, Pederson O. Suppression of GLUT4 expression in skeletal muscle of rats which are obese from high fat feeding but not from high carbohydrate feeding orgenetic obesity. Endocrinology, 1993, 132: 13-22
[113] Rosenblatt-Velin N, Lerch R, Papageorgiou I, Montessuit C. Insulin resistance in adult cardiomyocytes undergoing dedifferentiation: role of GLUT4 expression and translocation. FASEB J., 2004 May, 18(7): 872-4
[114] Mike Mueckler. Insulin resistance and the disruption of GLUT4 trafficking in skeletal muscle J Clin Invest, May 2001, 107(10): 1211-1213
[115] Wallberg-Henriksson H, Zierath JR. GLUT4: a key player regulating glucose homeostasis? Insights from transgenic and knockout mice. Mol Membr Biol, 2001 Jul-Sep, 18(3): 205-11
[116] Chalfie M., Tu Y. , Euskirchen G, Ward W W, et al. Green fluorescentprotein as a marker for gene expression. Science, 1994, 263: 802-805
[117] Prasher D. C. , et al. Primary structure of the Aequorea victoria green fluorescent protein. Gene, 1992, 111: 229-233
[118] Chalfie M., et al. Green fluorescent protein as a marker for gene expression. Science, 1994, 263: 802-805
[119] Inouye S. & Tsuji F. I. Aequorea green fluorescent protein: Expression of the gene and fluorescent characteristics of the recombinant protein. FEBS Letters, 1994, 341: 277-280
[120] Cormack B. et al. FACS-optimized mutants of the green fluorescent protein (GFP). Gene, 1996, 173: 33-38
[121] Haas J., et al. Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr Biol, 1996, 6: 315-324
[122] Matz M. V. , et al. Fluorescent proteins from nonbioluminescent Anthozoa species. Nature Biotech, 1999, 17: 969–973
[123] Gicquiaux H., Lecat S. , Gaire M. , et al. Rapid Internalization and Recycling of the Human Neuropeptide Y Y1 Receptor. J Biol Chem, 2002, 277: 6645 -6655
[124] Zunkler B. J. , Kuhne S. , Rustenbeck I. , et al. Mechanism of terfenadine block of ATP-sensitive K(+) channels. Br J Pharmacol, 2000, 130(7): 1571-4
[125] Lang T., Wacker I., Steyer rgen J., et al. Ca2+-Triggered Peptide Secretion Neurotechniquein Single Cells Imaged with Green FluorescentProtein and Evanescent-Wave Microscopy. Neuron, 1997, 18: 857–863
[126] Takuma T., Arakawa T., Okayama M., et al. Trafficking of green fluorescent protein-tagged SNARE proteins in HSY cells. J Biochem (Tokyo), 2002, 132(5): 729-35
[127] Schneider N. , Weber I. , Faix J. , et al. A Lim protein involved in the progression of cytokinesis and regulation of the mitotic spindle. Cell Motil Cytoskeleton, 2003, 56(2): 130-9
[128] Stanasila L., Perez J. B., Vogel H., et al. Oligomerization of the alpha1a and alpha1b-adrenergic receptor subtypes: potential implications in receptor internalization. J Biol Chem, 2003, 278(41): 40239-40251
[129] Tokunaga M, Yanagida T. Single molecule imaging of fluorophores and enzymatic reactions achieved by objective-type total internal reflection fluorescence microscopy. Biochem Biophys Res Commun, 1997, 235: 47–53
[130] Yoshikazu Suzuki, Tomomi Tani, Kazuo Sutoh, Shinji Kamimura. Imaging of the fluorescence spectrum of a single fluorescent molecule by prism-based spectroscopy. FEBS Letters, 2002, 512: 235-239
[131] Li Ma, Vytautas P. Bindokas, Andrey Kuznetsov. et. al. Direct imaging shows that insulin granule exocytosis occurs by complete vesicle fusion. PNAS, 2004, 101(25): 9266–9271
[132] Thompson NL, Lagerholm BC. Total internal reflection fluorescence: applications in cellular biophysics. Curr Opin Biotechnol. 1997; 8(1): 58-64.
[133] Cheezum MK, Walker WF, Guilford WH. Quantitative comparison of algorithms for tracking single fluorescent particles. Biophys J, 2001, 81(10): 2378-2388
[134] Petersen KF, Shulman GI. Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. Am J Cardiol, 2002, 90(5A): 11G-18G.
[135] Hirohito Sone, Hiroaki Suzuki, Akimitsu Takahashi and Nobuhiro Yamada. Disease model: hyperinsulinemia and insulin resistance. TRENDS in Molecular Medicine, 2001,7(7): 320-322
[136] Garvey WT. Glucose transport and NIDDM. Diabetes Care, 1992, 15(3): 396-417
[137] Bogan JS, Hendon N, McKee AE, Tsao TS, Lodish HF. Functional cloning of TUG as a regulator of GLUT4 glucose transporter trafficking. Nature, 2003, 425(10): 727-734
[138] Lampson MA, Schmoranzer J, Zeigerer A, Simon SM, McGraw TE. Insulin-regulated Release from the Endosomal Recycling Compartment Is Regulated by Budding of Specialized Vesicles. Mol Biol Cell, 2001, 12(11): 3489-3501
[139] Zeigerer A, Lampson MA, Karylowski O, Sabatini DD, Adesnik M, Ren M, McGraw TE. GLUT4 retention in adipocytes requires two intracellular insulin-regulated transport steps. Mol Biol Cell, 2002, 13(7): 2421-2435
[140] Molloy SS, Anderson ED, Jean F, Thomas G. Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis. Trends Cell Biol, 1999, 9(1): 28–35
[141] Xaing Y, Molloy SS, Thomas L, Thomas G. The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments. Mol Biol Cell, 2000, 11(4): 1257-1273
[142] Martin S, Ramm G, Lyttle CT, Meerloo T, Stoorvogel W, James DE. Biogenesis of insulin-responsive GLUT4 vesicles is independent of brefeldin A-sensitive trafficking. Traffic, 2000, 1(8): 652-660
[143] Palacios S, Lalioti V, Martinez-Arca S, Chattopadhyay S, Sandoval IV. Recycling of the insulin-sensitive glucose transporter GLUT4. Access of surface internalized GLUT4 molecules to the perinuclear storage compartment is mediated by the Phe5-Gln6-Gln7-Ile8 motif. J Biol Chem, 2001, 276(5): 3371-3383
[144] Jahn R, Lang T, Südhof TC. Membrane Fusion. Cell, 2003, 112(2): 519–533
[145] Hashiramoto M, James DE. Characterization of insulin-responsive GLUT4 vesicles isolated from 3T3-L1 adipocytes. Mol Cell Biol, 2000, 20(1): 416-427
[146] Ramm G, Slot JW, James DE, Stoorvogel W. Insulin recruits GLUT4 from specialized VAMP2-carrying vesicles as well as from the dynamic endosomal/trans-Golgi network in rat adipocytes. Mol Biol Cell, 2000, 11(12): 4079-4091
[147] Kues T, Dickmanns A, Luhrmann R, Peters R, Kubitscheck U. High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP observed by single particle tracking. Proc Natl Acad Sci U S A, 2001, 98(21): 12021-12026
[148] Goulian M, Simon SM. Tracking single proteins within cells. Biophys J, 2000, 79(10): 2188-2198
[149] Thompson RE, Larson DR, Webb WW. Precise nanometer localization analysis for individual fluorescent probes. Biophys J, 2002, 82(5): 2775-2783
[150] Olveczky BP, Periasamy N, Verkman AS. Mapping fluorophore distributions in three dimensions by quantitative multiple angle-total internal reflection fluorescence microscopy. Biophys J, 1997, 73(5): 2836-2847
[151] Steyer JA, Almers W. A real-time view of life within 100 nm of the plasma membrane. Nat Rev Mol Cell Biol, 2001, 2(4): 268-275
[152] Oheim, M, Stühmer M. Tracking chromaffin granules on their way through the actin cortex. Eur Biophys J, 2000, 29(2): 67-89
[153] Rizzuto R, Carrington W, Tuft RA. Digital imaging microscopy of living cells. Trends Cell Biol, 1998, 8(7): 288-292
[154] Steyer JA, Almers W. Tracking single secretory granules in live chromaffin cells by evanescent-field fluorescence microscopy. Biophys J, 1999, 76(4): 2262-2271
[155] Becherer U, Moser T, Stuhmer W, Oheim M. Calcium regulates exocytosis at the level of single vesicles. Nat Neurosci, 2003, 6(8): 846-853
[156] Lang T, Wacker I, Wunderlich I, Rohrbach A, Giese G, Soldati T, Almers W. Role of actin cortex in the subplasmalemmal transport of secretory granules in PC-12 cells. Biophys J, 2000, 78(6): 2863-2877
[157] Qian H, Sheetz MP, Elson EL. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys J, 1991, 60(10): 910-921
[158] Saxton MJ, Jacobson K. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct, 1997, 26: 373-399
[159] Saxton MJ. Single-particle tracking: the distribution of diffusion coefficients. Biophys J, 1997, 72(4): 1744-1753
[160] Ng YK, Lu X, Gulacsi A, Han W, Saxton MJ, Levitan ES. Unexpected mobility variation among individual secretory vesicles produces an apparent refractory neuropeptide pool. Biophys J, 2003, 84(6): 4127 –4134
[161] Liu LB, Omata W, Kojima I, Shibata H. Insulin Recruits GLUT4 from Distinct Compartments via Distinct Traffic Pathways with Differential Microtubule Dependence in Rat Adipocytes. J Biol Chem, 2003, 278(32): 30157-30169
[162] Johns LM, Levitan ES, Shelden EA, Holz RW, Axelrod D. Restriction of secretory granule motion near the plasma membrane of chromaffin cells. J Cell Biol, 2001, 153(4): 177-190
[163] Hirokawa N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science, 1998, 279(5350): 519-526
[164] Kamal A, Goldstein LS. Principles of cargo attachment to cytoplasmic motor proteins. Curr Opin Cell Biol, 2002, 14(1): 63-68
[165] Thorn, N. A. In vitro studies of the release mechanism for vasopressin in rats. Acta Endocrinol, 1966, 53: 644–654
[166] Burke, N., W. Han, D. Li, K. Takimoto, S. C. Watkins, and E. S. Levitan. Neuronal peptide release is limited by secretory granule mobility. Neuron, 1997, 19: 1095–1102
[167] 周镜然. Caveolin家族分子研究进展. 细胞生物学杂志, 2002: 338-342
[168] Ulrich Salzar and Rainer Prohaska. Stomatin, flotillin-1 and flotillin-2 are major integral proteins of erythrocyte lipid rafts. BLOOD, 2001, 97(4): 1141-1143
[169] Mukherjee, S., Zha, X., Tabas, I., and Maxfield, F.R.. Choles-terol distribution in living cells: fluorescence imaging using dehydroergosteol as a fluorescent cholesterol analog. Biophys. J., 1998, 75: 1915–1925
[170] Mayor, S., Rothberg, K.G., and Maxfield, F.R.. Sequestration of GPI-anchored proteins in Caveolae triggered by cross-linking. Science, 1994, 264: 1948–1951
[171] Chen, C.S., Martin, O.C., and Pagano, R.E.. Changes in the spectral properties of a plasma membrane lipid analog during the first seconds of endocytosis in living cells. Biophys. J., 1997, 72: 37–50
[172] Kenworthy, A.K., Petranova, N., and Edidin, M. High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. Mol. Biol. Cell , 2000: 1645–1655
[173] Vrljic, M., Nishimura, S.Y., Brasselet, S., Moerner, W.E., and McConnell, H.M.. Translational diffusion of individual class II MHC membrane proteins in cells. Biophys. J., 2002, 83: 2681–2692
[174] Anderson, R.G., and Jacobson, K. A role for lipid shells in targeting proteins to Caveolae, rafts, and other lipid domains. Science, 2002, 296: 1821–1825
[175] Zacharias, D.A., Violin, J.D., Newton, A.C., and Tsien, R.Y.. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science, 2002, 296: 913–916
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |