title: Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation.
abstract: 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-3β 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.
authors.affiliation: Department of Biology, Graduate School of Science, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Takano
authors.forename: Haruko
authors.initials: H
authors.lastname: Watanabe-Takano
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
authors.forename: Souichi
authors.initials: S
authors.lastname: Kurita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsujita
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Karatsu
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Endo
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D024510:Muscle Development; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012518:Sarcomeres / Q000378:metabolism*; D015398:Signal Transduction; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D000199:Actins; D009124:Muscle Proteins; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C035620:nebulin; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt