Plasma membrane wound repair is characterized by extensive membrane lipid and protein rearrangements in vascular endothelial cells
Plasma membrane wound repair is characterized by extensive membrane lipid and protein rearrangements in vascular endothelial cells
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DOI：
10.1016/j.bbamcr.2021.118991
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发表时间：
2021-04-12
影响因子：
5.1
通讯作者：
Gerke, Volker
中科院分区：
文献类型：
--
作者：
Ashraf, Arsila P. K.;Gerke, Volker
血管内皮细胞受到由血流和与白细胞相互作用引起的机械应力。应力发生在顶端，血管面对细胞表面，并导致膜破裂，必须重新密封，以确保细胞存活。为了模拟这一过程，我们开发了一种选择性诱导内皮细胞顶端质膜损伤的激光消融方案。我们发现，Ca 2+依赖性膜resealing启动后，这个创伤协议，并伴随着大量的膜脂质动力学在伤口部位的过程。具体而言，磷脂酰肌醇（4，5）-二磷酸、磷脂酰丝氨酸和磷脂酸在膜创伤处迅速积累，形成膜联蛋白（Anx）家族的Ca 2 +/磷脂结合蛋白的潜在相互作用平台，所述膜联蛋白（Anx）家族也在创伤后数秒内被募集。一个膜联蛋白，AnxA 2，和它的假定的结合伙伴S100 A11干扰膜resealing表明，钙依赖性膜联蛋白-磷脂相互作用是必需的有效的膜创伤修复内皮细胞。
Vascular endothelial cells are subject to mechanical stress resulting from blood flow and interactions with leukocytes. Stress occurs at the apical, vessel-facing cell surface and leads to membrane ruptures that have to be resealed to ensure cell survival. To mimic this process, we developed a laser ablation protocol selectively inducing wounds in the apical plasma membrane of endothelial cells. We show that Ca2+-dependent membrane resealing is initiated following this wounding protocol and that the process is accompanied by substantial membrane lipid dynamics at the wound site. Specifically, phosphatidylinositol (4,5)-bisphosphate, phosphatidylserine and phosphatidic acid rapidly accumulate at membrane wounds forming potential interaction platforms for Ca2+/phospholipid binding proteins of the annexin (Anx) family that are also recruited within seconds after wounding. Depletion of one annexin, AnxA2, and its putative binding partner S100A11 interferes with membrane resealing suggesting that Ca2+-dependent annexin-phospholipid interactions are required for efficient membrane wound repair in endothelial cells.