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

被引:145
作者
Boye, Theresa Louise [1 ]
Maeda, Kenji [1 ]
Pezeshkian, Weria [2 ]
Sonder, Stine Lauritzen [1 ]
Haeger, Swantje Christin [1 ]
Gerke, Volker [3 ]
Simonsen, Adam Cohen [2 ]
Nylandsted, Jesper [1 ]
机构
[1] Danish Canc Soc, Res Ctr, Unit Cell Death & Metab, Membrane Integr Grp, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
[2] Univ Southern Denmark, Dept Phys Chem & Pharm, Campusvej 55, DK-5230 Odense M, Denmark
[3] Univ Munster, Ctr Mol Biol Inflammat, Inst Med Biochem, Von Esmarch Str 56, D-48149 Munster, Germany
关键词
PLASMA-MEMBRANE; MECHANISMS;
D O I
10.1038/s41467-017-01743-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 micronsize 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.
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页数:11
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