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. (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.
K. Takano, H. Watanabe-Takano, S. Suetsugu, S. Kurita, K. Tsujita, S. Kimura, T. Karatsu, T. Takenawa, T. Endo, Nebulin and N-WASP cooperate to cause IGF-1–induced sarcomeric actin filament formation. Science 330, 1536–1540 (2010). [Abstract] [Full Text]