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.
Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle
N. Ariotti’s present address is Mark Wainwright Analytical Centre, University of New South Wales, Sydney, New South Wales, Australia.
R.D. Day’s present address is Institute for Marine and Antarctic Studies, University of Tasmania, Hobart, Tasmania, Australia.
K.A. Smith’s present address is Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
- Award Id(s): APP1156489,APP1099251
- Award Id(s): 1174145
- Award Id(s): DP200102559
- Award Id(s): CE140100036
- Award Id(s): CE200100029
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Harriet P. Lo, Ye-Wheen Lim, Zherui Xiong, Nick Martel, Charles Ferguson, Nicholas Ariotti, Jean Giacomotto, James Rae, Matthias Floetenmeyer, Shayli Varasteh Moradi, Ya Gao, Vikas A. Tillu, Di Xia, Huang Wang, Samira Rahnama, Susan J. Nixon, Michele Bastiani, Ryan D. Day, Kelly A. Smith, Nathan J. Palpant, Wayne A. Johnston, Kirill Alexandrov, Brett M. Collins, Thomas E. Hall, Robert G. Parton; Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle. J Cell Biol 6 December 2021; 220 (12): e201905065. doi: https://doi.org/10.1083/jcb.201905065
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