The AQP-3 water channel is a pivotal modulator of glycerol-induced chloride channel activation in nasopharyngeal carcinoma cells

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• 作者：Haifeng Zhang^a ; ¹ ; ^{zhf19841011@126.com" class="auth_mail" title="E-mail the corresponding author} ; Zhiqin Deng^b ; ^e ; ¹ ; Lili Yang^c ; ¹ ; Hai Luo^d ; ^e ; Shanwen Liu^b ; ^e ; Yuan Li^d ; ^e ; Yan Wei^d ; ^e ; Shuang Peng^d ; ^e ; Linyan Zhu^b ; Liwei Wang^d ; ^{twangliwei@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Lixin Chen^b ; ^{tchenlixin@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AQP-3 ; ClC-3 ; Chloride channels ; Glycerol ; Protein&ndash ; protein interaction
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：72
• 期：Complete
• 页码：89-99
• 全文大小：1310 K

文摘

Aquaporin (AQP) and chloride channels are ubiquitous in virtually all living cells, playing pivotal roles in cell proliferation, migration and apoptosis. We previously reported that AQP-3 aquaglyceroporin and ClC-3 chloride channels could form complexes to regulate cell volume in nasopharyngeal carcinoma cells. In this study, the roles of AQP-3 in their hetero-complexes were further investigated. Glycerol entered the cells via AQP-3 and induced two different Cl⁻ currents through cell swelling-dependent or -independent pathways. The swelling-dependent Cl⁻ current was significantly inhibited by pretreatment with CuCl₂ and AQP-3-siRNA. After siRNA-induced AQP-3 knock-down, the 140 mM glycerol isoosmotic solution swelled cells by 22% (45% in AQP-3-intact cells) and induced a smaller Cl⁻ current; this current was smaller than that activated by 8% cell volume swelling, which induced by the 140 mM glycerol hyperosmotic solution in AQP-3-intact cells. This suggests that the interaction between AQP-3 and ClC-3 plays an important role in cell volume regulation and that AQP-3 may be a modulator that opens volume-regulated chloride channels. The swelling-independent Cl⁻ current, which was activated by extracellular glycerol, was reduced by CuCl₂ and AQP-3-siRNA pretreatment. Dialyzing glycerol into cells via the pipette directly induced the swelling-independent Cl⁻ current; however this current was blocked by AQP-3 down-regulation, suggesting AQP-3 is essential for the opening of chloride channels. In conclusion, AQP-3 is the pathway for water, glycerol and other small solutes to enter cells, and it may be an essential modulator for the gating of chloride channels.