Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2021 Jan 21;12(1):495. doi: 10.1038/s41467-020-20804-x.
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.
肌联蛋白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转变,参与多核肌细胞的形成。在这里,我们基于肌联蛋白改变外膜小叶的自发曲率向更正值的假设,考虑了肌联蛋白作用的物理机制。我们从理论上预测,肌联蛋白产生外叶弹性应力,该应力传播到半融合隔膜并加速融合孔的形成。我们表明,肌联蛋白胞外域确实产生了脂质单层的正自发曲率。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该机制。在这两个过程中,肌联蛋白胞外域的作用与已知产生脂质单层正自发曲率的溶血磷脂酰胆碱非常相似。通过改变近端膜单层的自发曲率来控制半融合后阶段,可能会被用于多种融合过程。