The actomyosin cortex controls t-tubule remodeling in skeletal muscle
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Ana Raquel Pereira Silvia Di Francescantonio Ana da Rosa Soares Tianyang Liu Filomena A Carvalho Josie Liane Ferreira Graciano Leal Inês Faleiro Naoko Kogata Beatrice Labella Teresinha Evangelista Nuno C Santos Michael Way Carolyn A Moores Edgar R GomesAbstract
A network of plasma membrane invaginations called t-tubules plays an essential role in controlling calcium release from the endoplasmic reticulum at the triads during muscle contraction. Although the importance of t-tubules for muscle physiology is well established, and abnormalities are found in muscle disorders, the mechanisms that mediate t-tubule growth are unknown. We show that the actomyosin cortex beneath the plasma membrane, regulated by Arp2/3 complexes containing Arpc5, acts as a gatekeeper for the membrane availability during t-tubule growth. Enlarged t-tubules are formed upon disruption of Arpc5, impairing the synchronization between plasma membrane depolarization and calcium release. Knockout of Arpc5 in mouse skeletal muscle results in impaired locomotion and posture. Furthermore, we show that human triadopathy patients and Arpc5 knockout mice accumulate enlarged t-tubules. We propose that cortex-dependent membrane availability affects muscle function, offering a potential pathophysiological mechanism for muscle disorders.
Journal details
Journal
Science advances
Volume
12
Issue number
36
Pages
eaeb3209
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10.1126/sciadv.aeb3209
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Europe PubMed Central
42685205
Pubmed
42685205
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The publication was previously a preprint.
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