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

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 leads 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 causes 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 variants.