Filopodia powered by class x myosin promote fusion of mammalian myoblasts.
Filopodia powered by class x myosin promote fusion of mammalian myoblasts.
复制标题
由x类肌球蛋白驱动的丝状伪足促进哺乳动物成肌细胞的融合。
DOI：
10.7554/elife.72419
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发表时间：
2021-09-14
期刊：
影响因子：
7.7
通讯作者：
Sweeney HL
中科院分区：
文献类型：
--
作者：
Hammers DW;Hart CC;Matheny MK;Heimsath EG;Lee YI;Hammer JA 3rd;Cheney RE;Sweeney HL
骨骼肌纤维是由单核成肌细胞融合形成的多核细胞巨体。已经发现了参与成肌细胞融合的几种分子，与成肌细胞融合一致的指状突起也与融合过程有关。本文研究了这些细胞投射在肌肉细胞融合中的作用。我们证明这些投射是由 X 类肌球蛋白 (Myo10) 产生的丝状伪足，X 类肌球蛋白是一种专门针对丝状伪足的非常规肌球蛋白运动蛋白。我们进一步表明，Myo10 在分化的成肌细胞中高度表达，并且 Myo10 消融可抑制体外丝状伪足的形成和成肌细胞融合。在体内，Myo10 标记与杜氏肌营养不良症和急性肌肉损伤相关的再生肌纤维。在小鼠中，肌肉驻留干细胞（称为卫星细胞）有条件地丧失 Myo10，会严重损害出生后的肌肉再生。此外，在成肌细胞丝状伪足中检测到肌肉融合蛋白 Myomaker 和 Myomixer。这些数据表明，Myo10 驱动的丝状伪足促进多核哺乳动物肌肉的形成。
Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein. We demonstrate that these projections are filopodia generated by class X myosin (Myo10), an unconventional myosin motor protein specialized for filopodia. We further show that Myo10 is highly expressed by differentiating myoblasts, and Myo10 ablation inhibits both filopodia formation and myoblast fusion in vitro. In vivo, Myo10 labels regenerating muscle fibers associated with Duchenne muscular dystrophy and acute muscle injury. In mice, conditional loss of Myo10 from muscle-resident stem cells, known as satellite cells, severely impairs postnatal muscle regeneration. Furthermore, the muscle fusion proteins Myomaker and Myomixer are detected in myoblast filopodia. These data demonstrate that Myo10-driven filopodia facilitate multinucleated mammalian muscle formation.
影响因子：
4.4
作者：
Burghardt TP;Neff KL;Wieben ED;Ajtai K
通讯作者：
Ajtai K