Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle
Open Access
- 11 October 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (12)
- https://doi.org/10.1083/jcb.201905065
Abstract
The cavin proteins are essential for caveola biogenesis and function. Here, we identify a role for the muscle-specific component, Cavin4, in skeletal muscle T-tubule development by analyzing two vertebrate systems, mouse and zebrafish. In both models, Cavin4 localized to T-tubules, and loss of Cavin4 resulted in aberrant T-tubule maturation. In zebrafish, which possess duplicated cavin4 paralogs, Cavin4b was shown to directly interact with the T-tubule–associated BAR domain protein Bin1. Loss of both Cavin4a and Cavin4b caused aberrant accumulation of interconnected caveolae within the T-tubules, a fragmented T-tubule network enriched in Caveolin-3, and an impaired Ca2+ response upon mechanical stimulation. We propose a role for Cavin4 in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to the sarcolemma. This generates a stable T-tubule domain lacking caveolae that is essential for T-tubule function.Keywords
Funding Information
- National Health and Medical Research Council (APP1156489, APP1099251)
- National Health and Medical Research Council (1174145)
- Australian Research Council (DP200102559)
- Australian Research Council (CE140100036)
- Australian Research Council (CE200100029)
- CSIRO–Queensland University of Technology
- Australian Cancer Research Foundation
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