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Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation.

eLife (2023-04-21)
Eline Lemerle, Jeanne Lainé, Marion Benoist, Gilles Moulay, Anne Bigot, Clémence Labasse, Angéline Madelaine, Alexis Canette, Perrine Aubin, Jean-Michel Vallat, Norma B Romero, Marc Bitoun, Vincent Mouly, Isabelle Marty, Bruno Cadot, Laura Picas, Stéphane Vassilopoulos
ABSTRACT

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, Bin1 and caveolae composed of caveolin-3 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Bin1 expression 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 results in 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 dysfunction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-MURC antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab1
Sigma-Aldrich
Monoclonal Anti-α-Actinin (Sarcomeric) antibody produced in mouse, clone EA-53, ascites fluid
Sigma-Aldrich
Anti-Bin1, clone 99D (Ascites Free) Antibody, clone 99D, 1 mg/mL, from mouse