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

Eline Lemerle (1) , Jeanne Lainé (1) , Marion Benoist (1) , Gilles Moulay (1) , Anne Bigot (1) , Clémence Labasse (2) , Angéline Madelaine (2) , Alexis Canette (3) , Perrine Aubin (4) , Jean-Michel Vallat (5) , Norma Romero (2) , Marc Bitoun (1) , Vincent Mouly (1) , Isabelle Marty (6) , Bruno Cadot (1) , Laura Picas (7, 8) , Stéphane Vassilopoulos (1)

1 Centre de recherche en Myologie – U974 SU-INSERM
2 Institut de Myologie
3 IBPS-ME - Microscopie Electronique [IBPS]
4 UGA - Université Grenoble Alpes
5 Hôpital Dupuytren [CHU Limoges]
6 GIN - [GIN] Grenoble Institut des Neurosciences
7 IRIM - Institut de Recherche en Infectiologie de Montpellier
8 UM - Université de Montpellier

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.

Domains: Life Sciences [q-bio]

Eline Lemerle, Jeanne Lainé, Marion Benoist, Gilles Moulay, Anne Bigot, et al.. Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation. eLife, 2023, 12, ⟨10.7554/eLife.84139⟩. ⟨hal-04094370⟩