The actomyosin cortex controls t-tubule remodeling in skeletal muscle
- 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. Gomes
2026-09-02
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.