Sustained activation of N-WASP through phosphorylation is essential for neurite extension |
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Authors: | Suetsugu Shiro Hattori Mitsuharu Miki Hiroaki Tezuka Tohru Yamamoto Tadashi Mikoshiba Katsuhiko Takenawa Tadaomi |
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Institution: | Department of Biochemistry, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan. |
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Abstract: | Neurite extension is a key process for constructing neuronal circuits during development and remodeling of the nervous system. Here we show that Src family tyrosine kinases and proteasome degradation signals synergistically regulate N-WASP in neurite extension. Src family kinases activate N-WASP through tyrosine phosphorylation, which induces Arp2/3 complex-mediated actin polymerization. Tyrosine phosphorylation of N-WASP also initiates its degradation through ubiquitination. When neurite growth is stimulated in culture, degradation of N-WASP is markedly inhibited, leading to accumulation of the phosphorylated N-WASP. On the other hand, under culture conditions that inhibit neurite extension, but favor proliferation, the phosphorylated N-WASP is degraded rapidly. Collectively, neurite extension is regulated by the balance of N-WASP phosphorylation (activation) and degradation (inactivation), which are induced by tyrosine phosphorylation. |
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