Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm.
Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm.
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DOI：
10.1038/s41467-020-20804-x
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发表时间：
2021-01-21
影响因子：
16.6
通讯作者：
Chernomordik LV
中科院分区：
文献类型：
--
作者：
Golani G;Leikina E;Melikov K;Whitlock JM;Gamage DG;Luoma-Overstreet G;Millay DP;Kozlov MM;Chernomordik LV
Myomerger是一种肌肉特异性膜蛋白，通过介导从早期半融合阶段到完全融合的过渡，参与多核肌细胞的形成。在这里，我们考虑了Myomerger作用的物理机制，其假设是Myomerger将外膜瓣叶的自发曲率转变为更正值。我们从理论上预测，Myomerger产生外瓣叶弹性应力，该应力传播到半融合隔膜中并加速融合孔形成。我们发现，Myomerger胞外域确实产生积极的自发曲率的脂质单层。我们通过成肌细胞融合和流感血凝素介导的细胞融合实验证实了这一机制。在这两个过程中，Myomerger胞外域的影响是惊人的相似的溶血磷脂酰胆碱已知产生一个积极的自发曲率的脂质单层。通过改变近端膜单层的自发曲率来控制半融合后阶段可用于不同的融合过程。在多核肌细胞形成过程中，Myomerger介导从早期半融合阶段到完全融合的过渡。在这里，作者使用理论建模和细胞融合实验表明，Myomerger通过耦合成肌细胞膜的近端和远端小叶的弹性应力来促进融合孔。
Myomerger is a muscle-specific membrane protein involved in formation of multinucleated muscle cells by mediating the transition from the early hemifusion stage to complete fusion. Here, we considered the physical mechanism of the Myomerger action based on the hypothesis that Myomerger shifts the spontaneous curvature of the outer membrane leaflets to more positive values. We predicted, theoretically, that Myomerger generates the outer leaflet elastic stresses, which propagate into the hemifusion diaphragm and accelerate the fusion pore formation. We showed that Myomerger ectodomain indeed generates positive spontaneous curvature of lipid monolayers. We substantiated the mechanism by experiments on myoblast fusion and influenza hemagglutinin-mediated cell fusion. In both processes, the effects of Myomerger ectodomain were strikingly similar to those of lysophosphatidylcholine known to generate a positive spontaneous curvature of lipid monolayers. The control of post-hemifusion stages by shifting the spontaneous curvature of proximal membrane monolayers may be utilized in diverse fusion processes. Myomerger mediates the transition from the early hemifusion stage to complete fusion during the formation of multinucleated muscle cells. Here, authors use theoretical modeling and cell fusion experiments to show that Myomerger promotes a fusion pore by coupling the elastic stresses of the proximal and distal leaflets of myoblast membrane.
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DOI：
10.1039/c7cp01921a
发表时间：
2017-06-28
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Doktorova M;Harries D;Khelashvili G
通讯作者：
Khelashvili G
影响因子：
5.4
作者：
Gui, Long;Ebner, Jamie L.;Lee, Kelly K.
通讯作者：
Lee, Kelly K.
影响因子：
4.6
作者：
Kliesch TT;Dietz J;Turco L;Halder P;Polo E;Tarantola M;Jahn R;Janshoff A
通讯作者：
Janshoff A
影响因子：
4.8
作者：
Faust, Joseph E.;Desai, Tanvi;McNew, James A.
通讯作者：
McNew, James A.
影响因子：
4.5
作者：
Frolov, VA;Cho, MS;Zimmerberg, J
通讯作者：
Zimmerberg, J