Sustained activation of N-WASP through phosphorylation is essential for neurite extension.

Developmental cell

PubMedID: 12431372

Suetsugu S, Hattori M, Miki H, Tezuka T, Yamamoto T, Mikoshiba K, Takenawa T. Sustained activation of N-WASP through phosphorylation is essential for neurite extension. Dev Cell. 2002;3(5):645-58.
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.