Grewal Thomas, Hoque Monira, Conway James R W, Reverter Meritxell, Wahba Mohamed, Beevi Syed S, Timpson Paul, Enrich Carlos, Rentero Carles
a Faculty of Pharmacy , University of Sydney , Sydney , NSW , Australia.
b The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent's Clinical School, Faculty of Medicine , University of New South Wales , Sydney , NSW , Australia.
Cell Adh Migr. 2017 May 4;11(3):288-304. doi: 10.1080/19336918.2016.1268318. Epub 2017 Jan 6.
Annexin A6 (AnxA6) belongs to a highly conserved protein family characterized by their calcium (Ca)-dependent binding to phospholipids. Over the years, immunohistochemistry, subcellular fractionations, and live cell microscopy established that AnxA6 is predominantly found at the plasma membrane and endosomal compartments. In these locations, AnxA6 acts as a multifunctional scaffold protein, recruiting signaling proteins, modulating cholesterol and membrane transport and influencing actin dynamics. These activities enable AnxA6 to contribute to the formation of multifactorial protein complexes and membrane domains relevant in signal transduction, cholesterol homeostasis and endo-/exocytic membrane transport. Hence, AnxA6 has been implicated in many biological processes, including cell proliferation, survival, differentiation, inflammation, but also membrane repair and viral infection. More recently, we and others identified roles for AnxA6 in cancer cell migration and invasion. This review will discuss how the multiple scaffold functions may enable AnxA6 to modulate migratory cell behavior in health and disease.
膜联蛋白A6（AnxA6）属于一个高度保守的蛋白质家族，其特征是能依赖钙（Ca）与磷脂结合。多年来，免疫组织化学、亚细胞分级分离和活细胞显微镜观察证实，AnxA6主要存在于质膜和内体区室。在这些位置，AnxA6作为一种多功能支架蛋白，招募信号蛋白，调节胆固醇和膜运输，并影响肌动蛋白动力学。这些活动使AnxA6能够促进与信号转导、胆固醇稳态和内吞/外吐膜运输相关的多因素蛋白复合物和膜结构域的形成。因此，AnxA6参与了许多生物学过程，包括细胞增殖、存活、分化、炎症，以及膜修复和病毒感染。最近，我们和其他人确定了AnxA6在癌细胞迁移和侵袭中的作用。本综述将讨论多种支架功能如何使AnxA6在健康和疾病状态下调节迁移细胞行为。
