ESCRT-mediated machinery directly drives cardiac T-tubule formation

Cardiac transverse tubules (T-tubules) are regular spaced plasma membrane invaginations that play an essential role in establishing excitation-contraction coupling of cardiomyocytes, yet the molecular machinery that controls T-tubule formation remains elusive. The endosomal sorting complex required for transport (ESCRT) proteins are involved in a variety of cellular events primarily through regulating membrane deformation in a reverse topology mode (budding away from cytosol). Strikingly, we find ESCRT directly controls the inward budding of cardiomyocyte plasma membrane to form T-tubules. Visualization of postnatal cardiomyocytes uncovers the gradual localization of charged multivesicular body protein 4b (Chmp4b), the key ESCRT-III filament component, to T-tubules.