Membrane Integrity Group, Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Nat Commun. 2017 Nov 20;8(1):1623. doi: 10.1038/s41467-017-01743-6.
Efficient cell membrane repair mechanisms are essential for maintaining membrane integrity and thus for cell life. Here we show that the Ca- and phospholipid-binding proteins annexin A4 and A6 are involved in plasma membrane repair and needed for rapid closure of micron-size holes. We demonstrate that annexin A4 binds to artificial membranes and generates curvature force initiated from free edges, whereas annexin A6 induces constriction force. In cells, plasma membrane injury and Ca influx recruit annexin A4 to the vicinity of membrane wound edges where its homo-trimerization leads to membrane curvature near the edges. We propose that curvature force is utilized together with annexin A6-mediated constriction force to pull the wound edges together for eventual fusion. We show that annexin A4 can counteract various plasma membrane disruptions including holes of several micrometers indicating that induction of curvature force around wound edges is an early key event in cell membrane repair.
高效的细胞膜修复机制对于维持膜的完整性和细胞的生命至关重要。在这里，我们表明钙和磷脂结合蛋白 annexin A4 和 A6 参与了质膜修复，并需要快速封闭微米大小的孔。我们证明 annexin A4 结合到人工膜上，并从自由边缘产生曲率力，而 annexin A6 则诱导收缩力。在细胞中，质膜损伤和 Ca 内流将 annexin A4 募集到膜损伤边缘附近，其同源三聚体化导致边缘附近的膜弯曲。我们提出，曲率力与 annexin A6 介导的收缩力一起用于将伤口边缘拉到一起，最终融合。我们表明 annexin A4 可以抵抗各种质膜破坏，包括几微米的孔，这表明在质膜修复中，围绕伤口边缘诱导曲率力是早期的关键事件。
