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

Guiraud, Alexandre, Couturier, Nathalie, Christin, Emilie, Castellano, Léa, Daura, Marine, Kretz-Remy, Carole, Janin, Alexandre, Ghasemizadeh, Alireza, Del Carmine, Peggy, Monteiro, Laloe, Rotard, Ludivine, Sanchez, Colline, Jacquemond, Vincent, Burny, Claire, Janczarski, Stéphane, Durieux, Anne-Cécile, Arnould, David, Romero, Norma Beatriz, Bui, Mai Thao, Buchman, Vladimir L. ORCID: https://orcid.org/0000-0002-7631-8352, Julien, Laura, Bitoun, Marc and Gache, Vincent 2025. SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity. EMBO Reports 10.1038/s44319-025-00413-9

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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 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. [Abstract copyright: © 2025. The Author(s).]

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Biosciences
Publisher:	Springer
Date of First Compliant Deposit:	26 March 2025
Date of Acceptance:	18 February 2025
Last Modified:	26 Mar 2025 12:07
URI:	https://orca.cardiff.ac.uk/id/eprint/177172

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