Satellite cell-derived TRIM28 is pivotal for mechanical load- and injury-induced myogenesis.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-01 Epub Date: 2024-08-14 DOI:10.1038/s44319-024-00227-1

Kuan-Hung Lin, Jamie E Hibbert, Corey Gk Flynn, Jake L Lemens, Melissa M Torbey, Nathaniel D Steinert, Philip M Flejsierowicz, Kiley M Melka, Garrison T Lindley, Marcos Lares, Vijayasaradhi Setaluri, Amy J Wagers, Troy A Hornberger

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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.

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卫星细胞衍生的TRIM28对机械负荷和损伤诱导的肌肉生成至关重要。

卫星细胞是骨骼肌干细胞，有助于出生后的肌肉生长，它们赋予骨骼肌在严重损伤后再生的能力。在这里，我们发现卫星细胞的这种成肌潜能需要一种名为含三方基序 28（TRIM28）的蛋白质。有趣的是，与之前一项基于 C2C12 肌母细胞的研究中报道的作用不同，体外和体内的多种证据显示，TRIM28 的成肌功能并不依赖于其丝氨酸 473 残基的磷酸化变化。此外，TRIM28 的功能也不是通过调节卫星细胞的增殖或分化来实现的。相反，我们的研究结果表明，TRIM28 能够调节卫星细胞在融合过程中的进展。具体地说，我们发现 TRIM28 控制着一种叫做肌融合器的融合蛋白的表达以及随之而来的融合孔的形成。总之，这项研究的结果揭示了一种新的调控途径的框架，这种调控途径对肌形成至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.