Ferlin proteins in myoblast fusion and muscle growth.
Ferlin proteins in myoblast fusion and muscle growth.
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DOI：
10.1016/b978-0-12-385940-2.00008-5
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发表时间：
2011
影响因子：
--
通讯作者：
McNally, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Posey, Avery D., Jr.;Demonbreun, Alexis;McNally, Elizabeth M.
成肌细胞融合有助于成熟肌肉在发育和再生过程中的肌肉生长。成肌细胞彼此融合，并融合成多核肌管以扩大肌纤维。成肌细胞融合的分子机制还不完全清楚。粘附、并置和膜融合伴随着细胞骨架重排。ferlin蛋白家族与人类肌肉疾病有关，并与肌肉中的融合事件有关，包括成肌细胞融合、囊泡运输和膜修复。Dysferlin是第一个发现的哺乳动物ferlin，现在已知有六种不同的ferlin。dysferlin基因的功能缺失突变导致肢带型肌营养不良症和较轻的三好肌病。Dysferlin是一种膜相关蛋白，与肌肉质膜的再密封破坏有关。新的数据支持dysferlin在细胞内囊泡运动中发挥更广泛的作用，这一过程对重新密封也很重要。肌电传递蛋白在经历融合的成肌细胞中高度表达，并且肌电传递蛋白的缺乏导致受损的成肌细胞融合。Myoferlin还调节细胞内运输事件，包括内吞再循环，这是一个内化的囊泡返回质膜的过程。本文综述了ferlin蛋白的运输作用，特别关注这种机制如何改变肌肉发生和肌肉生长。
Myoblast fusion contributes to muscle growth in development and during regeneration of mature muscle. Myoblasts fuse to each other as well as to multinucleate myotubes to enlarge the myofiber. The molecular mechanisms of myoblast fusion are incompletely understood. Adhesion, apposition, and membrane fusion are accompanied by cytoskeletal rearrangements. The ferlin family of proteins is implicated in human muscle disease and has been implicated in fusion events in muscle, including myoblast fusion, vesicle trafficking and membrane repair. Dysferlin was the first mammalian ferlin identified and it is now know that there are six different ferlins. Loss of function mutations in the dysferlin gene lead to limb girdle muscular dystrophy and the milder disorder Miyoshi myopathy. Dysferlin is a membrane-associated protein that has been implicated in resealing disruptions in the muscle plasma membrane. Newer data supports a broader role for dysferlin in intracellular vesicular movement, a process also important for resealing. Myoferlin is highly expressed in myoblasts that undergoing fusion, and the absence of myoferlin leads to impaired myoblast fusion. Myoferlin also regulates intracellular trafficking events, including endocytic recycling, a process where internalized vesicles are returned to the plasma membrane. The trafficking role of ferlin proteins is reviewed herein with a specific focus as to how this machinery alters myogenesis and muscle growth.