Nebulin and N-WASP Cooperate to Cause IGF-1-Induced Sarcomeric Actin Filament Formation
Nebulin and N-WASP Cooperate to Cause IGF-1-Induced Sarcomeric Actin Filament Formation
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DOI：
10.1126/science.1197767
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发表时间：
2010-12-10
期刊：
影响因子：
56.9
通讯作者：
Endo, Takeshi
中科院分区：
文献类型：
--
作者：
Takano, Kazunori;Watanabe-Takano, Haruko;Endo, Takeshi
胰岛素样生长因子1（IGF-1）诱导骨骼肌成熟和扩大（肥大）。这些反应需要蛋白质合成和肌原纤维形成（肌原纤维发生）。然而，肌原纤维发生的信号转导机制仍不清楚。我们发现，IGF-1诱导的磷脂酰肌醇3-激酶-Akt信号通过干扰小鼠糖原合成酶激酶-3 β在肌原纤维的Z带形成了一个星云蛋白和N-WASP的复合物。尽管已知N-WASP是Arp 2/3复合物的激活剂以形成分支肌动蛋白丝，但在没有Arp 2/3复合物的情况下，星云蛋白-N-WASP复合物引起肌动蛋白成核以从Z带形成无分支肌动蛋白丝。此外，N-WASP是IGF-1诱导的肌肉肥大所必需的。这些发现提出了IGF-1诱导的肌动蛋白丝形成的机制，肌原纤维形成所需的肌肉成熟和肥大和肌动蛋白成核的机制。
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-3 beta 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.