1. Satellite cell-derived TRIM28 is pivotal for mechanical load- and injury-induced myogenesis.
- Author
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Lin, Kuan-Hung, Hibbert, Jamie E, Flynn, Corey GK, Lemens, Jake L, Torbey, Melissa M, Steinert, Nathaniel D, Flejsierowicz, Philip M, Melka, Kiley M, Lindley, Garrison T, Lares, Marcos, Setaluri, Vijayasaradhi, Wagers, Amy J, and Hornberger, Troy A
- Abstract
Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discover that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Interestingly, different from the role reported in a previous study based on C2C12 myoblasts, multiple lines of both in vitro and in vivo evidence reveal that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 are not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discover that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis. Synopsis: TRIM28 is pivotal for the myogenic potential of satellite cells by controlling the expression of myomixer and concomitant fusion pore formation. The knockout (KO) of TRIM28 in satellite cells attenuates mechanical load-induced myonuclear accretion, but it does not impact mechanical load-induced hypertrophy. The expression of TRIM28 in satellite cells is necessary for injury-induced myogenesis/regeneration. A novel in vivo "rescue" approach with human TRIM28 (hTRIM28) reveals that the myogenic function of TRIM28 is not dependent on changes in TRIM28(S473) phosphorylation. TRIM28 regulates myogenesis by controlling the induction of myomixer and concomitant fusion pore formation, but it is not required for the induction of myomaker and the process of hemifusion. TRIM28 is pivotal for the myogenic potential of satellite cells by controlling the expression of myomixer and concomitant fusion pore formation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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