The connexin 43 C-terminus: A tail of many tales
The connexin 43 C-terminus: A tail of many tales
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DOI：
10.1016/j.bbamem.2017.05.008
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Aasen, Trond
中科院分区：
文献类型：
--
作者：
Leithe, Edward;Mesnil, Marc;Aasen, Trond
连接蛋白是脊椎动物的间隙连接通道蛋白，通过使相邻细胞的细胞质之间能够直接通讯，创建了一个独特的细胞信号网络。间隙连接细胞间通讯（GJIC）在控制细胞生长和分化以及组织发育和内稳态方面具有重要作用。此外，还发现了几种与GJIC无关的非经典连接蛋白功能。在人类连接蛋白家族的21个成员中，连接蛋白43（Cx43）是表达最广泛且研究最多的。Cx43的长细胞质C末端（CT）受到广泛的翻译后修饰，这些修饰调节其细胞内运输和间隙连接通道的门控。此外，Cx43的C末端包含多个参与蛋白质相互作用的结构域，这些结构域允许Cx43与细胞骨架和调节蛋白之间发生串扰。这些结构域使Cx43具有独立于GJIC影响细胞生长和分化的能力。在此，我们综述了目前对Cx43的C末端的调节及其独特功能的理解，包括其作为全长Cx43的重要组成部分以及作为一个独立的信号枢纽的情况。我们强调了由Cx43的C末端控制的复杂调节和信号网络，包括作为间隙连接通道依赖性功能和非依赖性功能基础的广泛的蛋白质相互作用组。我们结合最近关于Cx43特定截短形式直接翻译的发现来讨论这些数据。本文是由让 - 克洛德·埃尔韦编辑的题为《间隙连接蛋白》的特刊的一部分。（c）2017爱思唯尔公司。保留所有权利。
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied. The long cytosolic C-terminus (CT) of Cx43 is subject to extensive post-translational modifications that modulate its intracellular trafficking and gap junction channel gating. Moreover, the Cx43 CT contains multiple domains involved in protein interactions that permit crosstalk between Cx43 and cytoskeletal and regulatory proteins. These domains endow Cx43 with the capacity to affect cell growth and differentiation independently of GJIC. Here, we review the current understanding of the regulation and unique functions of the Cx43 CT, both as an essential component of full-length Cx43 and as an independent signalling hub. We highlight the complex regulatory and signalling networks controlled by the Cx43 CT, including the extensive protein interactome that underlies both gap junction channel-dependent and-independent functions. We discuss these data in relation to the recent discovery of the direct translation of specific truncated forms of Cx43. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. (c) 2017 Elsevier B.V. All rights reserved.