Barrallo-Gimeno Alejandro, Gradogna Antonella, Zanardi Ilaria, Pusch Michael, Estévez Raúl
Sección de Fisiología, Departamento de Ciencias Fisiológicas II, University of Barcelona, Barcelona, Spain.
U-750, Centro de investigación en red de enfermedades raras (CIBERER), ISCIII, Barcelona, Spain.
J Physiol. 2015 Sep 15;593(18):4111-27. doi: 10.1113/JP270057.
The CLC family of chloride channels and transporters is composed by nine members, but only three of them, ClC-Ka/b, ClC-7 and ClC-2, have been found so far associated with auxiliary subunits. These CLC regulatory subunits are small proteins that present few common characteristics among them, both structurally and functionally, and their effects on the corresponding CLC protein are different. Barttin, a protein with two transmembrane domains, is essential for the membrane localization of ClC-K proteins and their activity in the kidney and inner ear. Ostm1 is a protein with a single transmembrane domain and a highly glycosylated N-terminus. Unlike the other two CLC auxiliary subunits, Ostm1 shows a reciprocal relationship with ClC-7 for their stability. The subcellular localization of Ostm1 depends on ClC-7 and not the other way around. ClC-2 is active on its own, but GlialCAM, a transmembrane cell adhesion molecule with two extracellular immunoglobulin (Ig)-like domains, regulates its subcellular localization and activity in glial cells. The common theme for these three proteins is their requirement for a proper homeostasis, since their malfunction leads to distinct diseases. We will review here their properties and their role in normal chloride physiology and the pathological consequences of their improper function.
氯离子通道和转运体的CLC家族由九个成员组成，但迄今为止，仅发现其中三个成员（ClC-Ka/b、ClC-7和ClC-2）与辅助亚基相关。这些CLC调节亚基是小蛋白，在结构和功能上几乎没有共同特征，并且它们对相应CLC蛋白的影响也不同。Barttin是一种具有两个跨膜结构域的蛋白，对于ClC-K蛋白在肾脏和内耳中的膜定位及其活性至关重要。Ostm1是一种具有单个跨膜结构域和高度糖基化N端的蛋白。与其他两个CLC辅助亚基不同，Ostm1与ClC-7在稳定性方面呈现相互关系。Ostm1的亚细胞定位取决于ClC-7，反之则不然。ClC-2自身具有活性，但GlialCAM是一种具有两个细胞外免疫球蛋白（Ig）样结构域的跨膜细胞粘附分子，可调节其在神经胶质细胞中的亚细胞定位和活性。这三种蛋白的共同特点是它们对适当的稳态的需求，因为它们的功能异常会导致不同的疾病。我们将在此处综述它们的特性、在正常氯离子生理学中的作用以及其功能异常的病理后果。
