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Publication : Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.

First Author  Takano K Year  2010
Journal  Science Volume  330
Issue  6010 Pages  1536-40
PubMed ID  21148390 Mgi Jnum  J:167290
Mgi Id  MGI:4867766 Doi  10.1126/science.1197767
Citation  Takano K, et al. (2010) Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation. Science 330(6010):1536-40
abstractText  Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis and myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3beta in mice. Although N-WASP is known to be an activator of the Arp2/3 complex to form branched actin filaments, the nebulin-N-WASP complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-WASP was required for IGF-1-induced muscle hypertrophy. These findings present the mechanisms of IGF-1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation.
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