Mukai Atsushi, Kurisaki Tomohiro, Sato Satoshi B, Kobayashi Toshihide, Kondoh Gen, Hashimoto Naohiro
Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Morioka, Oobu, Aichi 474-8522, Japan.
Exp Cell Res. 2009 Oct 15;315(17):3052-63. doi: 10.1016/j.yexcr.2009.07.010. Epub 2009 Jul 14.
Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, beta-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.
最近的研究表明，成肌细胞（成肌细胞和肌管）的片状伪足前沿含有假定的融合位点，但使质膜具有融合能力的机制仍基本未知。在这里，我们表明脂筏的动态聚集和分散在成肌细胞融合过程中对细胞黏附和质膜结合都有贡献。包括M-钙黏蛋白、β-连环蛋白和p120-连环蛋白在内的黏附复合体蛋白在细胞接触前以脂筏依赖的方式聚集在片状伪足的前沿，该前沿包含质膜的假定融合位点。此外，胆固醇耗竭破坏脂筏直接阻止了成肌细胞融合的膜结合。延时记录显示，在膜融合前，脂筏从片状伪足中心横向分散。当脂筏横向分散时，聚集在脂筏上的黏附蛋白也从假定的融合位点被移除。前沿由此产生的无脂筏和黏附复合体区域与相对的质膜融合。这些结果证明了脂筏的动态聚集/分散在建立成肌细胞膜的融合能力位点中起关键作用，为成肌细胞融合的调控提供了新的机制见解。
