Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility
Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility
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DOI：
10.1016/j.ydbio.2010.07.014
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发表时间：
2010-10-01
影响因子：
2.7
通讯作者：
Pointis, Georges
中科院分区：
文献类型：
--
作者：
Carette, Diane;Weider, Karola;Pointis, Georges
在不同的上皮细胞中，细胞膜相互接触形成细胞间连接复合物，包括紧密连接、粘附连接和间隙连接，它们可以相互影响彼此的表达。我们在此利用条件性支持细胞敲除Cx43（SCCx 43 KO（-/-））转基因小鼠和特异性抗Cx43 siRNA研究了Cx43在粘附蛋白和紧密连接蛋白（N-cadherin，beta-catenin，occludin和ZO-1）调控中的作用。与野生型睾丸相比，SCCx 43 KO（-/-）中的间隙连接偶联和Cx43水平降低。超微结构分析显示，SCCx 43 KO（-/-）睾丸中间隙连接消失，紧密连接和粘附连接的存在以及血睾屏障的持续完整性。与野生型动物相比，在SCCx 43 KO（-/-）小鼠中封闭蛋白、N-钙粘蛋白和β-连环蛋白水平增强，而ZO-1水平降低。Cx43 siRNA阻断了支持细胞中的间隙连接功能，并改变了紧密和粘附蛋白水平。紧密连接和粘附连接的Cx43控制似乎是通道依赖性的，因为间隙连接阻断剂（大黄酸和油酰胺）导致类似的结果。这些数据表明，由Cx43的精子发生的控制可能介导的支持细胞Cx43通道，这是必需的，不仅在支持细胞和生殖细胞之间的细胞/细胞通信，但也在其他连接蛋白的调节所必需的血-睾丸屏障。(C)2010年爱思唯尔公司All rights reserved.
In different epithelia, cell membranes contacting one another form intercellular junctional complexes including tight, adherens and gap junctions, which could mutually influence the expression of each other. We have here investigated the role of Cx43 in the control of adherens and tight junction proteins (N-cadherin, beta-catenin, occludin and ZO-1) by using conditional Sertoli cell knockout Cx43 (SCCx43KO(-/-)) transgenic mice and specific anti-Cx43 siRNA. Gap junction coupling and Cx43 levels were reduced in SCCx43KO(-/-) as compared to Wild-type testes. Ultrastructural analysis revealed disappearance of gap junctions, the presence of tight and adherens junctions and persistent integrity of the blood-testis barrier in SCCx43KO(-/-) testis. Occludin, N-cadherin and beta-catenin levels were enhanced in SCCx43KO(-/-) mice as compared to Wild-type animals whereas ZO-1 levels were reduced. Cx43 siRNA blocked gap junction functionality in Sertoli cells and altered tight and adherens protein levels. The Cx43 control of tight and adherens junctions appeared channel-dependent since gap junction blockers (glycyrrhetinic acid and oleamide) led to similar results. These data suggest that the control of spermatogenesis by Cx43 may be mediated through Sertoli cell Cx43 channels, which are required, not only in cell/cell communication between Sertoli and germ cells, but also in the regulation of other junctional proteins essential for the blood-testis barrier. (C) 2010 Elsevier Inc. All rights reserved.