RT Journal Article
SR Electronic
T1 Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.01.514746
DO 10.1101/2022.11.01.514746
A1 Eline Lemerle
A1 Jeanne Lainé
A1 Gilles Moulay
A1 Anne Bigot
A1 Clémence Labasse
A1 Angeline Madelaine
A1 Alexis Canette
A1 Perrine Aubin-Tessier
A1 Jean-Michel Vallat
A1 Norma Romero
A1 Marc Bitoun
A1 Vincent Mouly
A1 Isabelle Marty
A1 Bruno Cadot
A1 Laura Picas
A1 Stéphane Vassilopoulos
YR 2022
UL http://biorxiv.org/content/early/2022/11/03/2022.11.01.514746.abstract
AB Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of a plasma membrane invagination, the T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although the precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in T-tubule formation and mutations of several of their constituents induce muscle weakness and myopathies. Here, we demonstrate that, at the plasma membrane, caveolae composed of caveolin-3 and Bin1 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Overexpression of Bin1 lead to the formation of both rings and tubes and we show that Bin1 forms scaffolds on which caveolae accumulate to form the initial T-tubule. Cav3 deficiency caused by either gene silencing or pathogenic mutations cause defective ring formation and perturbed Bin1-mediated tubulation that may explain defective T-tubule organization in mature muscles. Our results uncover new pathophysiological mechanisms that may prove relevant to myopathies caused by Cav3 or Bin1.Competing Interest StatementThe authors have declared no competing interest.