Author:
Lo Harriet P.,Lim Ye-Wheen,Xiong Zherui,Martel Nick,Ferguson Charles,Ariotti Nicholas R.,Giacomotto Jean,Rae James A.,Floetenmeyer Matthias,Moradi Shayli Varasteh,Gao Ya,Tillu Vikas A.,Xia Di,Wang Huang,Rahnama Samira,Nixon Susan J.,Bastiani Michele,Day Ryan D.,Smith Kelly A.,Palpant Nathan J.,Johnston Wayne A.,Alexandrov Kirill,Collins Brett M.,Hall Thomas E.,Parton Robert G.
Abstract
SummaryThe 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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