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). We demonstrate that Chmp4b is essential for T-tubule formation, a process dependent on the ESCRT-I component Tsg101. Our results uncover that the spatiotemporal organization of ESCRT can orchestrate invaginations of cardiomyocyte plasma membrane.