Blood-brain barrier defects associated with Rbp9 mutation

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• 作者：Jihyun Kim (2)
  Young-Joon Kim (1)
  Jeongsil Kim-Ha (2)
  
• 关键词：adhesion ; blood brain barrier ; Drosophila ; elav ; Rbp9
• 刊名：Molecules and Cells
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：29
• 期：1
• 页码：93-98
• 全文大小：326KB
• 参考文献：1. Bainton, R.J., Tsai, L.T., Schwabe, T., DeSalvo, M., Gaul, U., and Heberlein, U. (2005). Moody encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in / Drosophila. Cell / 123, 145鈥?56. CrossRef
  2. Baumgartner, S., Littleton, J.T., Broadie, K., Bhat, M.A., Harbecke, R., Lengyel, J.A., Chiquet-Ehrismann, R., Prokop, A., and Bellen, H.J. (1996). A / Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function. Cell / 87, 1059鈥?068. CrossRef
  3. Carlson, S.D., Juang, J.L., Hilgers, S.L., and Garment, M.B. (2000). Blood barriers of the insect. Annu. Rev. Entomol. / 45, 151鈥?74. CrossRef
  4. Driscoll, M., and Gerstbrein, B. (2003). Dying for a cause: invertebrate genetics takes on human meurodegeneration. Nat. Rev. Genet. / 4, 181鈥?94. CrossRef
  5. Einheber, S., Zanazzi, G., Ching, W., Scherer, S., Milner, T.A., Peles, E., and Salzer, J.L. (1997). The axonal membrane protein Caspr, a homologue of neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination. J. Cell Biol. / 139, 1495鈥?506. CrossRef
  6. Feany, M.B., and Bender, W.W. (2000). A / Drosophila model of Parkinson鈥檚 disease. Nature / 404, 394鈥?98. CrossRef
  7. Halter, D.A., Urban, J., Rickert, C., Ner, S.S., Ito, K., Travers, A.A., and Technau, G.M. (1995). The homeobox gene / repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of / Drosophila melanogaster. Development / 121, 317鈥?32.
  8. Honnorat, J., and Cartalat-Carel, S. (2004). Advances in paraneoplastic neurological syndromes. Curr. Opin. Oncol. / 16, 614鈥?20. CrossRef
  9. Igarashi, Y., Utsumi, H., Chiba, H., Yanada-Sasamori, Y., Tobioka, H., Kamimura, Y., Furuuchi, K., Kokai, Y., Nakagawa, T., Mori, M., et al. (1999). Glial cell line derived neurotrophic factor induces barrier function of endothelial cells forming the bloodbrain barrier. Biochem. Biophys. Res. Commun. / 261, 108鈥?12. CrossRef
  10. Jeong, K., and Kim-Ha, J. (2004). Precocious expression of / Drosophila Rbp9 inhibits ovarian germ cell proliferation. Mol. Cells / 18, 230鈥?36.
  11. Kim, Y.J., and Baker, B.S. (1993). The / Drosophila gene / Rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous system-specific in both flies and humans. J. Neurosci. / 13, 1045鈥?056.
  12. Kim, S.N., Rhee, J.H., Song, Y.H., Park, D.Y., Hwang, M., Lee, S.L., Kim, J.E., Gim, B.S., Yoon, J.H., Kim, Y.J., et al. (2005). Age-dependent changes of gene expression in the / Drosophila head. Neurobiol. Aging / 26, 1083鈥?091. CrossRef
  13. Kim-Ha, J., Kim, J., and Kim, Y.J. (1999). Requirement of / RBP9, a / Drosophila Hu homolog, for regulation of cystocyte differentiation and oocyte determination during oogenesis. Mol. Cell. Biol. / 19, 2505鈥?504.
  14. Koushika, S.P., Lisbin, M.J., and White, K. (1996). / ELAV, a / Drosophila neuron-specific protein, mediates the generation of an alternatively spliced neural protein isoform. Curr. Biol. / 6, 1634鈥?641. CrossRef
  15. Koushika, S.P., Soller, M., and White, K. (2000). The neuron-enriched splicing pattern of / Drosophila erect wing is dependent on the presence of / ELAV protein. Mol. Cell. Biol. / 20, 1836鈥?845. CrossRef
  16. Mayer, F., Mayer, N., Chinn, L., Pinsonneault, R.L., Kroetz, D., and Bainton, R. (2009). Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in / Drosophila. J. Neurosci. / 29, 3538鈥?550. CrossRef
  17. Nelson, B., Nishimura, S., Kanuka, H., Kuranaga, E., Inoue, M., Hori, G., Nakahara, H., and Miura, M. (2005). Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration. Cell Death Differ. / 12, 1115鈥?123. CrossRef
  18. Palladino, M.J., Hadley, T.J., and Genetzky, B. (2002). Temperature-sensitive paralytic mutants are enriched for those causing neurodegeneration in / Drosophila. Genetics / 161, 1197鈥?208.
  19. Park, S.J., Yang, E.S., Kim-Ha, J., and Kim, Y.J. (1998). Down regulation of extramachrochaetae mRNA by a / Drosophila neural RNA binding protein / Rbp9 which is homologous to human Hu proteins. Nucleic Acids Res. / 26, 2989鈥?994. CrossRef
  20. Robinow, S., and White, K. (1988). The locus / elav of / Drosophila melanogaster is expressed in neurons at all developmental stages. Dev. Biol. / 126, 294鈥?03. CrossRef
  21. Robinow, S., and White, K. (1991). Characterization and spatial distribution of the / ELAV protein during / Drosophila melanogaster development. J. Neurobiol. / 22, 443鈥?61. CrossRef
  22. Russell, A.B., and Carlson, S.S. (1997). Neurexin is expressed on nerves, but not at nerve terminals, in the electric organ. J. Neurosci. / 17, 4734鈥?743.
  23. Sarov-Blat, L., So, W.V., Liu, L., and Rosbash, M. (2000). The / Drosophila takeout gene is a novel molecular link between circadian rhythms and feeding behavior. Cell / 101, 647鈥?56. CrossRef
  24. Stanely, P., McDowall, A., Bates, P.A., Brashaw, J., and Hogg, N. (2000). The second domain of intercellular adhesion molecule-1(ICAM-1) maintains the structural integrity of the leucocyte function-associated antigen-1 (LFA-1) ligand-binding site in the first domain. Biochem. J. / 351, 79鈥?6. CrossRef
  25. Stanewsky, R. (2003). Genetic analysis of the circadian system in / Drosophila melanogaster and mammals. J. Neurobiol. / 54, 111鈥?47. CrossRef
  26. Stork, T., Engelen, D., Krudewig, A., Silies, M., Bainton, R.J., and Klambt, C. (2008). Organization and function of the blood-brain barrier in / Drosophila. J. Neurosci. / 28, 587鈥?97. CrossRef
  
• 作者单位：Jihyun Kim (2)
  Young-Joon Kim (1)
  Jeongsil Kim-Ha (2)
  
  2. Department of Molecular Biology, College of Life Sciences, Sejong University, Seoul, 143-747, Korea
  1. Department of Biochemistry, Yonsei University, Seoul, 120-749, Korea
  
• ISSN：0219-1032

文摘

Rbp9 is a Drosophila RNA-binding protein that shares a high level of sequence similarity with Drosophila elav and human Hu proteins. Loss of function alleles of elav are embryonic lethal causing abnormal central nervous system (CNS) development, and Hu is implicated in the development of paraneoplastic neurological syndrome associated with small cell lung cancer. To elucidate the role of Rbp9, we generated Rbp9 mutant flies and examined them for symptoms related to paraneoplastic encephalomyelitis. Although Rbp9 proteins begin to appear from the middle of the pupal period in the cortex of the CNS, the Rbp9 mutants showed no apparent defects in development. However, as the mutant adult flies grew older, they showed reduced locomotor activities and lived only one-half of the life expectancy of wild-type flies. To understand the molecular mechanism underlying this symptom, gene expression profiles in Rbp9 mutants were analyzed and potential target genes were further characterized. Reduced expression of cell adhesion molecules was detected, and defects in the blood-brain barrier (BBB) of Rbp9 mutant brains could be seen. Putative Rbp9-binding sites were found in introns of genes that function in cell adhesion. Therefore, Rbp9 may regulate the splicing of cell adhesion molecules, critical for the formation of the BBB.