BIN1 modulation in vivo rescues dynamin-related myopathy
Valentina M. Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, R. Gómez, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xènia Massana-Muñoz, Nadège Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte
Abstract
Significance Membrane remodeling and trafficking is essential for intracellular organization under normal conditions and can be altered in a plethora of diseases. Here we characterized the action of amphiphysin (BIN1) and dynamin (DNM2), two main regulators of membrane remodeling mutated in congenital myopathies. We found their interplay is necessary for membrane fission in vitro and to maintain muscle homeostasis in vivo. Moreover, increasing BIN1 expression was validated as a therapeutic approach to ameliorate both mild and severe forms of DNM2-associated myopathies in mice.