Mutations in connexin 32: the molecular and biophysical bases for the X-linked form of Charcot-Marie-Tooth disease
Mutations in connexin 32: the molecular and biophysical bases for the X-linked form of Charcot-Marie-Tooth disease
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DOI：
10.1016/s0165-0173(99)00082-x
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发表时间：
2000-04-01
影响因子：
--
通讯作者：
Bargiello, TA
中科院分区：
文献类型：
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作者：
Abrams, CK;Oh, S;Bargiello, TA
连接蛋白是同源整合膜蛋白家族，其形成通道，所述通道为电信号的传输以及小离子和非电解质在偶联细胞之间的扩散提供低电阻途径。编码连接蛋白32（Cx 32）的基因中携带突变的个体（一种在结旁环和髓鞘形成的许旺细胞的施密特-兰特曼切口中表达的间隙连接蛋白）发展为周围神经病变-X连锁形式的夏科-马里-图思病（CMTX）。已经鉴定了超过160种与CMTX相关的Cx 32不同突变。一些突变将导致功能完全丧失，不可能表达功能通道。Cx 32中的一些突变导致Cx 32蛋白在细胞质中的异常积累，特别是在高尔基体中; CMTX可能由于Cx 32的不正确运输或干扰其他蛋白质的运输而出现。另一方面，Cx 32的许多突变形式可以形成功能通道。一些功能突变体的电导-电压关系被破坏到一定程度，这将导致大量减少可用的g-V关系。在其中一种情况下（Ser 26 Leu），连接介导的通信途径。其他的则具有基本上正常的稳态g-V关系。在这些情况之一（Ser 26 Leu）中，由突变引入的唯一变化是孔径从野生型通道的7埃减小到Ser 26 Leu的小于3埃。这种孔径的减小可能会限制重要信号分子的通过。这些研究结果表明，在某些情况下，如果不是所有的情况下，正常Cx 32的功能丧失足以导致CMTX，（C）2000爱思唯尔科学B. V.保留所有权利。
The connexins are a family of homologous integral membrane proteins that form channels that provide a low resistance pathway for the transmission of electrical signals and the diffusion of small ions and non-electrolytes between coupled cells. Individuals carrying mutations in the gene encoding connexin 32 (Cx32), a gap junction protein expressed in the paranodal loops and Schmidt-Lantermann incisures of myelinating Schwann cells, develop a peripheral neuropathy - the X-linked form of Charcot-Marie-Tooth disease (CMTX). Over 160 different mutations in Cx32 associated with CMTX have been identified. Some mutations will lead to complete loss of function with no possibility of expression of functional channels. Some mutations in Cx32 lead to the abnormal accumulation of Cx32 proteins in the cytoplasm, particularly in the Golgi apparatus; CMTX may arise due to incorrect trafficking of Cx32 or to interference with trafficking of other proteins. On the other hand, many mutant forms of Cx32 can form functional channels. Some functional mutants have conductance voltage relationships that are disrupted to a degree which would lead to a substantial reduction in the available g-V relations. In one of these cases (Ser26Leu), junction mediated communication pathway. Others have essentially normal steady-state g-V relations. In one of these cases (Ser26Leu), the only change introduced by the mutation is a reduction in the pore diameter from 7 Angstrom for the wild-type channel to less than 3 Angstrom tor Ser26Leu. This reduction in pore diameter may restrict the passage of important signaling molecules. These findings suggest that in some, if not all cases of CMTX, loss of function of normal Cx32 is sufficient to cause CMTX, (C) 2000 Elsevier Science B.V. All rights reserved.