Muscle-specific Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle

Lo, H.; Lim, Y.-W.; Xiong, Z.; Martel, N.; Ferguson, C.; Ariotti, N.; Giacomotto, J.; Rae, J.; Floetenmeyer, M.; Moradi, S. V.; Gao, Y.; Tillu, V.; Xia, D.; Wang, H.; Rahnama, S.; Nixon, S.; Bastiani, M.; Day, R.; Smith, K.; Palpant, N.; Johnston, W.; Alexandrov, K.; Collins, B.; Hall, T.; Parton, R.

doi:10.1101/2021.01.13.426456

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bioRxiv · 10.1101/2021.01.13.426456

Muscle-specific Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle

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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.

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Lo, H., Lim, Y.-W., Xiong, Z., Martel, N., Ferguson, C., Ariotti, N., Giacomotto, J., Rae, J., Floetenmeyer, M., Moradi, S. V., Gao, Y., Tillu, V., Xia, D., Wang, H., Rahnama, S., Nixon, S., Bastiani, M., Day, R., Smith, K., Palpant, N., Johnston, W., Alexandrov, K., Collins, B., Hall, T., Parton, R.. 2021-01-15. Muscle-specific Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle. https://doi.org/10.1101/2021.01.13.426456

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