Suetsugu Shiro, Hattori Mitsuharu, Miki Hiroaki, Tezuka Tohru, Yamamoto Tadashi, Mikoshiba Katsuhiko, Takenawa Tadaomi
Department of Biochemistry, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.
Dev Cell. 2002 Nov;3(5):645-58. doi: 10.1016/s1534-5807(02)00324-6.
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.
神经突延伸是神经系统发育和重塑过程中构建神经回路的关键过程。在此我们表明，Src家族酪氨酸激酶和蛋白酶体降解信号在神经突延伸过程中协同调节N-WASP。Src家族激酶通过酪氨酸磷酸化激活N-WASP，从而诱导Arp2/3复合物介导的肌动蛋白聚合。N-WASP的酪氨酸磷酸化还通过泛素化启动其降解。当在培养中刺激神经突生长时，N-WASP的降解受到明显抑制，导致磷酸化的N-WASP积累。另一方面，在抑制神经突延伸但有利于增殖的培养条件下，磷酸化的N-WASP迅速降解。总体而言，神经突延伸由酪氨酸磷酸化诱导的N-WASP磷酸化（激活）和降解（失活）的平衡所调节。
