Annexin A6 in the liver: From the endocytic compartment to cellular physiology
Annexin A6 in the liver: From the endocytic compartment to cellular physiology
复制标题
DOI：
10.1016/j.bbamcr.2016.10.017
复制
发表时间：
2017-06-01
影响因子：
5.1
通讯作者：
Grewal, Thomas
中科院分区：
文献类型：
--
作者：
Enrich, Carlos;Rentero, Carles;Grewal, Thomas
膜联蛋白A6（Annexin A6，AnxA 6）属于膜联蛋白家族，是一类钙离子依赖性膜结合蛋白。AnxA 6是所有膜联蛋白中最大的，并且在平滑肌、肝细胞、内皮细胞和心肌细胞中高度表达。激活后，AnxA 6在广泛的细胞内定位中结合带负电荷的磷脂，特别是质膜、晚期内体/前溶酶体，以及突触囊泡和肌膜。在这些细胞位点，AnxA 6被认为有助于组织膜微结构域，如富含胆固醇的脂筏，并赋予多种调节功能，从囊泡融合，胞吞和胞吐到程序性细胞死亡和肌肉收缩。越来越多的证据支持Ca 2+和Ca 2+结合蛋白控制内吞和自噬。它们的调节作用似乎在启动自噬的信号通路水平上或在自噬体与内溶酶体室融合的后期阶段起作用。自噬囊泡和内吞囊泡与溶酶体的融合具有几个特征，这些特征取决于源自溶酶体/晚期内体的Ca 2+，并且似乎取决于随后被该阳离子激活的蛋白质。然而，在这些自噬和内吞阶段的Ca 2+及其效应蛋白的参与仍然知之甚少。虽然AnxA 6占肝脏总蛋白的0.25%，但对其在肝细胞中的功能知之甚少。在内吞途径中，我们在肝细胞的内体和自噬体中鉴定了AnxA 6。因此，AnxA 6和其他可能的膜联蛋白可能代表新的Ca 2+效应器，调节肝细胞自噬和内吞运输的收敛步骤。本文是由Claus Heizmann、Joachim Krebs和Jacques Haiech编辑的题为：ECS会议的特刊的一部分。(C)2016爱思唯尔B. V.保留所有权利。
Annexin A6 (AnxA6) belongs to the conserved annexin family - a group of Ca2+-dependent membrane binding proteins. AnxA6 is the largest of all annexins and highly expressed in smooth muscle, hepatocytes, endothelial cells and cardiomyocytes. Upon activation, AnxA6 binds to negatively charged phospholipids in a wide range of intracellular localizations, in particular the plasma membrane, late endosomes/pre-lysosomes, but also synaptic vesicles and sarcolemma. In these cellular sites, AnxA6 is believed to contribute to the organization of membrane microdomains, such as cholesterol-rich lipid rafts and confer multiple regulatory functions, ranging from vesicle fusion, endocytosis and exocytosis to programmed cell death and muscle contraction. Growing evidence supports that Ca2+ and Ca2+-binding proteins control endocytosis and autophagy. Their regulatory role seems to operate at the level of the signalling pathways that initiate autophagy or at later stages, when autophagosomes fuse with endolysosomal compartments. The convergence of the autophagic and endocytic vesicles to lysosomes shares several features that depend on Ca2+ originating from lysosomes/late endosomes and seems to depend on proteins that are subsequently activated by this cation. However, the involvement of Ca2+ and its effector proteins in these autophagic and endocytic stages still remains poorly understood. Although AnxA6 makes up almost 0.25% of total protein in the liver, little is known about its function in hepatocytes. Within the endocytic route, we identified AnxA6 in endosomes and autophagosomes of hepatocytes. Hence, AnxA6 and possibly other annexins might represent new Ca2+ effectors that regulate converging steps of autophagy and endocytic trafficking in hepatocytes. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. (C) 2016 Elsevier B.V. All rights reserved.