Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.
Nat Commun. 2011;2:270. doi: 10.1038/ncomms1270.
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 Ca(2+) 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 Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.
真核细胞拥有一种通用的修复机制，可以确保细胞膜迅速修复破损。在修复之前，撕裂的细胞膜会承受相当大的张力，这种张力的作用是扩大破损。本文研究表明，钙激活后能在膜上自组装成二维（2D）结构的膜联蛋白 A5（AnxA5）能促进膜修复。与野生型小鼠血管周围细胞相比，AnxA5 缺失细胞的膜修复缺陷严重。向 AnxA5 缺失细胞中添加 AnxA5 可特异性结合到破损的膜区域，可挽救膜修复。相比之下，缺乏形成 2D 结构能力的 AnxA5 突变体则无法促进膜修复。本文提出了一个新的观点，即 AnxA5 参与了膜修复过程中的一个先前未知的步骤：钙局部内流触发后，AnxA5 蛋白与撕裂的膜边缘结合形成 2D 结构，从而防止伤口扩大并促进膜封闭。
