Slow myosin heavy chain 1 is required for slow myofibril and muscle fibre growth but not for myofibril initiation.
Slow myosin heavy chain 1 is required for slow myofibril and muscle fibre growth but not for myofibril initiation.
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DOI：
10.1016/j.ydbio.2023.04.002
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发表时间：
2023-07
影响因子：
2.7
通讯作者：
Hughes, Simon M.
中科院分区：
文献类型：
--
作者：
Hau, Hoi-Ting A.;Kelu, Jeffrey J.;Ochala, Julien;Hughes, Simon M.
慢肌球蛋白重链1（Smyhc1）是斑马鱼中驱动缓慢骨骼肌纤维早期收缩的主要肌节肌球蛋白。新的突变等位基因缺乏一个功能smyhc1基因移动差，但恢复运动性，后来形成的快速肌纤维的节段肌节成熟，是成人可行的。通过运动分析和抑制快速肌肉收缩试验，我们发现，缓慢的肌肉运动缺陷持续突变体，直到约1个月的年龄。在用EGFP标记慢肌纤维的遗传背景上育种揭示，突变慢肌纤维经历与野生型无区别的末端分化、迁移和纤维形成，但不能产生大的肌原纤维并保持细胞取向和附着。在突变体中，尽管存在替代的肌球蛋白重链分子，但具有1.67 μm周期性肌动蛋白带的初始肌原纤维结构不能成熟为野生型中观察到的1.96 μm肌节。收缩性差的突变型慢肌细胞产生许多细胞质细胞器，但不能生长和束肌原纤维或增加细胞质体积，尽管由快肌施加的被动运动。数据表明，缓慢的肌原纤维成熟和细胞体积的增加取决于一个特定的肌球蛋白亚型的功能，并建议适当的生产力调节肌纤维的生长。敲除smyhc1可使斑马鱼从轻度早期运动缺陷中恢复。肌节肌球蛋白免疫反应性的残余肌原纤维存在于慢肌纤维中。Smyhc1的缺乏大大降低了肌原纤维形成的程度，并减少了幼虫缓慢的纤维体积生长。
Slow myosin heavy chain 1 (Smyhc1) is the major sarcomeric myosin driving early contraction by slow skeletal muscle fibres in zebrafish. New mutant alleles lacking a functional smyhc1 gene move poorly, but recover motility as the later-formed fast muscle fibres of the segmental myotomes mature, and are adult viable. By motility analysis and inhibiting fast muscle contraction pharmacologically, we show that a slow muscle motility defect persists in mutants until about 1 month of age. Breeding onto a genetic background marking slow muscle fibres with EGFP revealed that mutant slow fibres undergo terminal differentiation, migration and fibre formation indistinguishable from wild type but fail to generate large myofibrils and maintain cellular orientation and attachments. In mutants, initial myofibrillar structures with 1.67 μm periodic actin bands fail to mature into the 1.96 μm sarcomeres observed in wild type, despite the presence of alternative myosin heavy chain molecules. The poorly-contractile mutant slow muscle cells generate numerous cytoplasmic organelles, but fail to grow and bundle myofibrils or to increase in cytoplasmic volume despite passive movements imposed by fast muscle. The data show that both slow myofibril maturation and cellular volume increase depend on the function of a specific myosin isoform and suggest that appropriate force production regulates muscle fibre growth. Knockout of smyhc1 yields viable zebrafish that recover from a mild early motility defect. Residual myofibrils with sarcomeric myosin immunoreactivity are present in slow muscle fibers. The absence of Smyhc1 greatly reduces the extent of myofibril formation and reduces larval slow fiber volumetric growth.
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影响因子：
3.7
作者：
Codina M;Li J;Gutiérrez J;Kao JP;Du SJ
通讯作者：
Du SJ
影响因子：
2.7
作者：
CONDON, K;SILBERSTEIN, L;THOMPSON, WJ
通讯作者：
THOMPSON, WJ
DOI：
10.1083/jcb.139.5.1219
发表时间：
1997-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Acakpo-Satchivi LJ;Edelmann W;Sartorius C;Lu BD;Wahr PA;Watkins SC;Metzger JM;Leinwand L;Kucherlapati R
通讯作者：
Kucherlapati R
DOI：
10.1152/ajpheart.00274.2002
发表时间：
2002-10-01
影响因子：
4.8
作者：
Alpert, NR;Brosseau, C;Warshaw, DM
通讯作者：
Warshaw, DM
影响因子：
4.6
作者：
Hinits, Yaniv;Hughes, Simon M.
通讯作者：
Hughes, Simon M.