SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-10 DOI:10.1038/s44319-025-00413-9

Alexandre Guiraud, Nathalie Couturier, Emilie Christin, Léa Castellano, Marine Daura, Carole Kretz-Remy, Alexandre Janin, Alireza Ghasemizadeh, Peggy Del Carmine, Laloe Monteiro, Ludivine Rotard, Colline Sanchez, Vincent Jacquemond, Claire Burny, Stéphane Janczarski, Anne-Cécile Durieux, David Arnould, Norma Beatriz Romero, Mai Thao Bui, Vladimir L Buchman, Laura Julien, Marc Bitoun, Vincent Gache

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引用次数: 0

Abstract

Dynamic changes in the arrangement of myonuclei and the organization of the sarcoplasmic reticulum are important determinants of myofiber formation and muscle function. To find factors associated with muscle integrity, we perform an siRNA screen and identify SH3KBP1 as a new factor controlling myoblast fusion, myonuclear positioning, and myotube elongation. We find that the N-terminus of SH3KBP1 binds to dynamin-2 while the C-terminus associates with the endoplasmic reticulum through calnexin, which in turn control myonuclei dynamics and ER integrity, respectively. Additionally, in mature muscle fibers, SH3KBP1 contributes to the formation of triads and modulates the Excitation-Contraction Coupling process efficiency. In Dnm2^R465W/+ mice, a model for centronuclear myopathy (CNM), depletion of Sh3kbp1 expression aggravates CNM-related atrophic phenotypes and impaired autophagic flux in mutant skeletal muscle fiber. Altogether, our results identify SH3KBP1 as a new regulator of myofiber integrity and function.

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SH3KBP1通过ER/SR结构完整性促进骨骼肌纤维形成和功能。

肌核排列和肌浆网组织的动态变化是肌纤维形成和肌肉功能的重要决定因素。为了找到与肌肉完整性相关的因素，我们进行了siRNA筛选，发现SH3KBP1是一个控制成肌细胞融合、肌核定位和肌管延伸的新因子。我们发现SH3KBP1的n端与动力蛋白-2结合，而c端通过钙连联蛋白与内质网结合，从而分别控制肌核动力学和内质网完整性。此外，在成熟肌纤维中，SH3KBP1有助于形成三联体并调节兴奋-收缩耦合过程的效率。在中心核肌病（CNM）模型Dnm2R465W/+小鼠中，Sh3kbp1表达的缺失加重了CNM相关的萎缩表型和突变骨骼肌纤维的自噬流量受损。总之，我们的研究结果确定SH3KBP1是肌纤维完整性和功能的新调节剂。

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.