Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair.

Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair.
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膜联蛋白A4和A6在细胞膜修复过程中诱导膜弯曲和收缩。

DOI:
10.1038/s41467-017-01743-6
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发表时间:
2017-11-20
影响因子:
16.6
通讯作者:
Nylandsted J
Nylandsted J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Boye TL;Maeda K;Pezeshkian W;Sønder SL;Haeger SC;Gerke V;Simonsen AC;Nylandsted J

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有效的细胞膜修复机制对于维持膜完整性和细胞生命至关重要。在这里,我们表明,Ca2+和磷脂结合蛋白膜联蛋白A4和A6参与质膜修复,需要快速关闭微米大小的孔。我们证明,膜联蛋白A4结合到人工膜,并产生弯曲力从自由边缘开始,而膜联蛋白A6诱导收缩力。在细胞中,质膜损伤和Ca2+内流将膜联蛋白A4募集到膜伤口边缘附近,在该处其同源三聚化导致边缘附近的膜弯曲。我们建议,曲率力与膜联蛋白A6介导的收缩力一起使用,以将伤口边缘拉到一起,最终融合。我们表明,膜联蛋白A4可以抵消各种质膜破坏,包括几个微米的孔,表明伤口边缘周围的曲率力的诱导是细胞膜修复的早期关键事件。膜联蛋白在细胞膜修复中的作用在很大程度上是不确定的。在这里,作者使用模型脂质双层来表明膜联蛋白A4诱导膜自由边缘的曲率,膜联蛋白A6诱导收缩力,并发现两种膜联蛋白都被招募到细胞中的伤口边缘,并且是修复所需的。
Efficient cell membrane repair mechanisms are essential for maintaining membrane integrity and thus for cell life. Here we show that the Ca2+- 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 Ca2+ 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. The role of annexins in cell membrane repair is largely undefined. Here the authors use a model lipid bilayer to show that annexin A4 induces curvature at the membrane free edge and annexin A6 induces constriction force, and find that both annexins are recruited to wound edges in cells and are required for repair.
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