Laboratory of Lipid Biochemistry, Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland.
Cell Mol Life Sci. 2012 Jun;69(11):1773-85. doi: 10.1007/s00018-011-0894-0. Epub 2011 Dec 13.
Growing evidence suggests that membrane microdomains enriched in cholesterol and sphingomyelin are sites for numerous cellular processes, including signaling, vesicular transport, interaction with pathogens, and viral infection, etc. Recently some members of the annexin family of conserved calcium and membrane-binding proteins have been recognized as cholesterol-interacting molecules and suggested to play a role in the formation, stabilization, and dynamics of membrane microdomains to affect membrane lateral organization and to attract other proteins and signaling molecules onto their territory. Furthermore, annexins were implicated in the interactions between cytosolic and membrane molecules, in the turnover and storage of cholesterol and in various signaling pathways. In this review, we focus on the mechanisms of interaction of annexins with lipid microdomains and the role of annexins in membrane microdomains dynamics including possible participation of the domain-associated forms of annexins in the etiology of human lysosomal storage disease called Niemann-Pick type C disease, related to the abnormal storage of cholesterol in the lysosome-like intracellular compartment. The involvement of annexins and cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes mellitus, and cancer is likely, but is not supported by substantial experimental observations, and therefore awaits further clarification.
越来越多的证据表明，富含胆固醇和鞘磷脂的膜微区是许多细胞过程的发生部位，包括信号转导、囊泡运输、与病原体的相互作用以及病毒感染等。最近，一些膜联蛋白家族的保守钙和膜结合蛋白已被认为是与胆固醇相互作用的分子，并被认为在膜微区的形成、稳定和动态中发挥作用，从而影响膜的侧向组织，并吸引其他蛋白质和信号分子进入其领域。此外，膜联蛋白还参与了细胞质和膜分子之间的相互作用、胆固醇的周转和储存以及各种信号通路。在这篇综述中，我们重点讨论了膜联蛋白与脂质微区相互作用的机制，以及膜联蛋白在膜微区动力学中的作用，包括域相关形式的膜联蛋白可能参与人类溶酶体贮积病（称为尼曼-匹克 C 型疾病）的发病机制，该疾病与溶酶体样细胞内隔室中胆固醇的异常储存有关。膜联蛋白和富含胆固醇/鞘磷脂的膜微区在其他病理学中的作用，包括心脏功能障碍、神经退行性疾病、肥胖、糖尿病和癌症，很可能存在，但尚未得到实质性实验观察的支持，因此需要进一步澄清。
