期刊
SCIENCE SIGNALING
卷 6, 期 265, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2003661
关键词
-
资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Japanese Ministry of Health, Labor, and Welfare
- Astellas Foundation
- Kowa Life Science Foundation
- Mochida Foundation
- Takeda Science Foundation
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [23650200] Funding Source: KAKEN
During neuronal development, axons navigate long distances, eventually forming precise connections with such targets as peripheral tissues. Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. We found that phosphorylation of Ser(1194) in Dock6 inhibited its GEF activity and suppressed axonal growth of embryonic sensory neurons and axon regeneration of postnatal sensory neurons in vitro and in vivo. At early developmental stages, when axons are growing, the protein phosphatase PP2A interacted with and dephosphorylated Dock6, thereby increasing the activity of Dock6. At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching. Thus, the phosphorylation status of Dock6 at Ser(1194) determines whether it promotes axon extension or branching in sensory neurons, revealing interplay between kinase and phosphatase action on a Rho-GEF during axon growth.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据