MG53 nucleates assembly of cell membrane repair machinery.
MG53 nucleates assembly of cell membrane repair machinery.
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DOI：
10.1038/ncb1812
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发表时间：
2009-01
影响因子：
21.3
通讯作者：
Ma, Jianjie
中科院分区：
文献类型：
--
作者：
Cai, Chuanxi;Masumiya, Haruko;Weisleder, Noah;Matsuda, Noriyuki;Nishi, Miyuki;Hwang, Moonsun;Ko, Jae-Kyun;Lin, Peihui;Thornton, Angela;Zhao, Xiaoli;Pan, Zui;Komazaki, Shinji;Brotto, Marco;Takeshima, Hiroshi;Ma, Jianjie
动态膜修复和重塑是维持细胞完整性和介导有效细胞功能的基本过程。在这里，我们报告说，MG 53，肌肉特异性的三方基序家族蛋白（TRIM 72），是肌膜膜修复机制的组成部分。MG 53与磷脂酰丝氨酸相互作用以与细胞内囊泡缔合，所述细胞内囊泡运输至肌膜并与肌膜融合。MG 53缺失的小鼠表现出进行性肌病和运动能力下降，与膜修复能力缺陷相关。肌膜的损伤导致细胞外氧化环境的进入和MG 53寡聚化，导致含有MG 53的囊泡募集到损伤部位。在囊泡易位后，细胞外Ca 2+的进入促进囊泡融合以重新密封膜。我们的数据表明，胞内囊泡易位和Ca2+依赖性膜融合是不同的步骤参与膜损伤的修复，MG 53可能会启动组装的膜修复机制在氧化依赖性的方式。
Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca2+ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca2+-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.
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