EMBO reports · 2025
SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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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, Julien Laura, Bitoun Marc, Gache Vincent
Аннотация
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 Dnm2R465W/+ 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.