Nebulin and N-WASP Cooperate to Cause IGF-1–Induced Sarcomeric Actin Filament Formation

Abstract

Muscle Building The signaling mechanisms involved in actin filament formation for myofibril formation, which is required for growth factor-induced muscle maturation and hypertrophy, remain unclear. Takano et al. (p. 1536 ; see the Perspective by Gautel and Ehler ) now show that the mechanism involves the interaction of nebulin and N-WASP. N-WASP is an activator of the Arp2/3 complex, which induces branched actin filaments in nonmuscle cells. The nebulin–N-WASP complex formed in muscle, however, causes nucleation of unbranched actin filaments within myofibrils without the Arp2/3 complex. Nebulin–N-WASP–mediated myofibrillar actin filament formation is required for muscle hypertrophy and might explain a congenital hereditary neuromuscular disorder caused by nebulin gene mutation: nemaline myopathy.