Argenzio Elisabetta, Moolenaar Wouter H
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands
J Cell Sci. 2016 Nov 15;129(22):4165-4174. doi: 10.1242/jcs.189795.
Cl intracellular channels (CLICs) are a family of six evolutionary conserved cytosolic proteins that exist in both soluble and membrane-associated forms; however, their functions have long been elusive. Soluble CLICs adopt a glutathione S-transferase (GST)-fold, can induce ion currents in artificial membranes and show oxidoreductase activity in vitro, but there is no convincing evidence of CLICs having such activities in vivo. Recent studies have revealed a role for CLIC proteins in Rho-regulated cortical actin dynamics as well as vesicular trafficking and integrin recycling, the latter of which are under the control of Rab GTPases. In this Commentary, we discuss the emerging roles of CLIC proteins in these processes and the lessons learned from gene-targeting studies. We also highlight outstanding questions regarding the molecular function(s) of these important but still poorly understood proteins.
氯离子细胞内通道蛋白（CLICs）是一个由六种进化上保守的胞质蛋白组成的家族，它们以可溶性和膜相关形式存在；然而，其功能长期以来一直难以捉摸。可溶性CLICs具有谷胱甘肽S-转移酶（GST）样结构，能在人工膜中诱导离子电流，并在体外显示氧化还原酶活性，但没有令人信服的证据表明CLICs在体内具有此类活性。最近的研究揭示了CLIC蛋白在Rho调节的皮质肌动蛋白动力学以及囊泡运输和整合素循环中的作用，其中后者受Rab GTP酶的控制。在本述评中，我们讨论了CLIC蛋白在这些过程中新兴的作用以及基因靶向研究的经验教训。我们还强调了关于这些重要但仍了解不足的蛋白的分子功能的突出问题。
