Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis
Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol homeostasis
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DOI：
10.1016/j.biocel.2009.12.020
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发表时间：
2010-05-01
影响因子：
4
通讯作者：
Enrich, Carlos
中科院分区：
文献类型：
--
作者：
Grewal, Thomas;Koese, Meryem;Enrich, Carlos
膜联蛋白A6（Annexin A6，AnxA 6）属于高度保守的膜联蛋白家族。与其他膜联蛋白一样，AnxA 6的功能与其以Ca（2+）依赖性方式结合磷脂的能力有关，从而以动态、可逆和受调节的方式与细胞膜相互作用。在细胞活化后，AnxA 6被募集到质膜、内体和小窝/膜筏，与信号蛋白、内吞机制和肌动蛋白细胞骨架相互作用，以抑制表皮生长因子受体和Ras信号传导。此外，AnxA 6与晚期内体结合以调节胆固醇输出，导致细胞质磷脂酶A2活性降低和小窝形成。因此，AnxA 6可能作为膜结构域的组织者发挥作用，（i）为多因子信号复合物的形成创建支架，（ii）在内吞转运过程中调节瞬时膜-肌动蛋白相互作用，以及（iii）调节细胞内胆固醇稳态。总之，这将调节关键的生理过程，包括增殖，分化，炎症和细胞迁移。(C)2010爱思唯尔有限公司保留所有权利。
Annexin A6 (AnxA6) belongs to the highly conserved annexin protein family. Like other annexins, the function of AnxA6 is linked to its ability to bind phospholipids in a Ca(2+)-dependent manner, thereby interacting with cellular membranes in a dynamic, reversible and regulated fashion. Upon cell activation, AnxA6 is recruited to the plasma membrane, endosomes and caveolae/membrane rafts to interact with signalling proteins, the endocytic machinery and actin cytoskeleton to inhibit epidermal growth factor receptor and Ras signalling. In addition, AnxA6 associates with late endosomes to regulate cholesterol export leading to reduced cytoplasmic phospholipase A2 activity and caveolae formation. Accordingly, AnxA6 may function as an organizer of membrane domains (i) to create a scaffold for the formation of multifactorial signalling complexes, (ii) to regulate transient membrane-actin interactions during endocytic transport, and (iii) to modulate intracellular cholesterol homeostasis. Altogether, this will regulate critical physiological processes including proliferation, differentiation, inflammation and cell migration. (C) 2010 Elsevier Ltd. All rights reserved.