Annexin-V stabilizes membrane defects by inducing lipid phase transition
Annexin-V stabilizes membrane defects by inducing lipid phase transition
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DOI：
10.1038/s41467-019-14045-w
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发表时间：
2020-01-13
影响因子：
16.6
通讯作者：
Scheuring, Simon
中科院分区：
文献类型：
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作者：
Lin, Yi-Chih;Chipot, Christophe;Scheuring, Simon
膜联蛋白是丰富的细胞质蛋白，其以Ca 2+依赖性方式结合至暴露带负电荷的磷脂的膜。在细胞损伤期间，细胞外Ca 2+的进入激活膜联蛋白膜结合能力，随后启动膜修复过程。然而，膜联蛋白在膜修复中的机制作用在很大程度上仍然未知。在这里，我们使用高速原子力显微镜（HS-AFM），荧光恢复后的光漂白（FRAP），共聚焦激光扫描显微镜（CLSM）和分子动力学模拟（MDS）来分析膜联蛋白V（A5）如何结合到磷脂酰丝氨酸（PS）丰富的膜导致高Ca 2+浓度的膜，然后在动态和组织的脂质的变化，最终膜相变。A5自组装成晶格进一步稳定并可能将膜结构化成凝胶相。我们的研究结果是兼容的补丁resealing通过囊泡融合机制在膜修复，并表明，A5保留带负电荷的脂质内小叶在受伤的细胞。
Annexins are abundant cytoplasmic proteins, which bind to membranes that expose negatively charged phospholipids in a Ca2+-dependent manner. During cell injuries, the entry of extracellular Ca2+ activates the annexin membrane-binding ability, subsequently initiating membrane repair processes. However, the mechanistic action of annexins in membrane repair remains largely unknown. Here, we use high-speed atomic force microscopy (HS-AFM), fluorescence recovery after photobleaching (FRAP), confocal laser scanning microscopy (CLSM) and molecular dynamics simulations (MDSs) to analyze how annexin-V (A5) binds to phosphatidylserine (PS)-rich membranes leading to high Ca2+-concentrations at membrane, and then to changes in the dynamics and organization of lipids, eventually to a membrane phase transition. A5 self-assembly into lattices further stabilizes and likely structures the membrane into a gel phase. Our findings are compatible with the patch resealing through vesicle fusion mechanism in membrane repair and indicate that A5 retains negatively charged lipids in the inner leaflet in an injured cell.