Key result
Cavin4 loss in animal models fragments T-tubule networks and impairs Ca2+ response to mechanical stimulation.
Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle by remodeling the T-tubule membrane.
Cavin4-Bin1 interaction supports T-tubule stability in models; leaves open relevance to human muscle disorders.
Summary 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 Ca 2+ 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 et al. (2021) studied Skeletal muscle T-tubule development. Cavin4 loss vs. Wild-type was evaluated on T-tubule maturation and Ca2+ response. Loss of Cavin4 in mouse and zebrafish models caused aberrant accumulation of interconnected caveolae, fragmented T-tubule networks, and impaired Ca2+ response upon mechanical stimulation.
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