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

Harriet P. Lo, Ye-Wheen Lim, Zherui Xiong, Nick Martel, Charles Ferguson, , , James Rae, Matthias Floetenmeyer, Shayli Varasteh Moradi
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Published: 11 October 2021

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: function / proteins / tubule / caveolae / zebrafish / loss / Cavin4b / skeletal / models

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