Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.

Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.
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DOI:
10.1038/ncomms1270
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发表时间:
2011
影响因子:
16.6
通讯作者:
Brisson AR
Brisson AR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bouter A;Gounou C;Bérat R;Tan S;Gallois B;Granier T;d'Estaintot BL;Pöschl E;Brachvogel B;Brisson AR

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真核细胞拥有一种通用的修复机制,确保质膜破裂的快速重新密封。在重新密封之前,撕裂的薄膜受到相当大的张力,这会扩大破坏的程度。在这里,我们展示了膜联蛋白-A5(AnxA5),一种在钙离子激活时在膜上自组装成二维(2D)阵列的蛋白质,促进了膜修复。与野生型小鼠血管周围细胞相比,AnxA5缺失细胞表现出严重的膜修复缺陷。AnxA5的加入挽救了AnxA5缺失细胞的膜修复,AnxA5仅与破坏的膜区域结合。相反,缺乏形成2D阵列能力的AnxA5突变体无法促进膜修复。我们认为AnxA5参与了膜修复过程中一个以前未知的步骤:在局部钙离子内流的触发下,AnxA5蛋白结合到撕裂的膜边缘,形成2D阵列,防止伤口扩张,促进膜重新密封。真核细胞质膜具有修复机械应力等刺激引起的撕裂的机制。作者证明,当在钙存在的情况下组装成二维阵列时,膜联蛋白-A5是膜修复所必需的。
Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing. Eukaryotic cell plasma membranes possess a mechanism to repair tears caused by stimuli such as mechanical stress. The authors demonstrate that annexin-A5, when assembled into two-dimensional arrays in the presence of calcium, is required for membrane repair.
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