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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.
Item Type: | Article |
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Authors/Creators: | Lo, HP and Lim, Y-W and Xiong, Z and Martel, N and Ferguson, C and Ariotti, N and Giacomotto, J and Rae, J and Floetenmeyer, M and Moradi, SV and Gao, Y and Tillu, VA and Xia, D and Wang, H and Rahnama, S and Nixon, SJ and Bastiani, M and Day, RD and Smith, KA and Palpant, NJ and Johnston, WA and Alexandrov, K and Collins, BM and Hall, TE and Parton, RG |
Keywords: | skeletal muscle, cavin proteins, Cavin4 |
Journal or Publication Title: | Journal of Cell Biology |
Publisher: | Rockefeller Univ Press |
ISSN: | 0021-9525 |
DOI / ID Number: | https://doi.org/10.1083/jcb.201905065 |
Copyright Information: | © 2021 Lo et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
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