RhoA/ROCK regulation of neuritogenesis via profilin IIa-mediated control of actin stability

被引:190
作者
Da Silva, JS
Medina, M
Zuliani, C
Di Nardo, A
Witke, W
Dotti, CG
机构
[1] Univ Turin, Cavalieri Ottolenghi Sci Inst, I-10043 Turin, Italy
[2] German Canc Res Ctr, Tumor Immunol Programme, D-69120 Heidelberg, Germany
[3] European Mol Biol Lab, Mouse Biol Programme, I-00016 Monterotondo, Italy
关键词
neuronal differentiation; hippocampal neurons; actin dynamics; Rho GTPases; actin-binding proteins;
D O I
10.1083/jcb.200304021
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Neuritogenesis, the first step of neuronal differentiation, takes place as nascent neurites bud from the immediate postmitotic neuronal soma. Little is known about the mechanisms underlying the dramatic morphological changes that characterize this event. Here, we show that RhoA activity plays a decisive role during neuritogenesis of cultured hippocampal neurons by recruiting and activating its specific kinase ROCK, which, in turn, complexes with profilin IIa. We establish that this previously uncharacterized brain-specific actin-binding protein controls neurite sprouting by modifying actin stability, a function regulated by ROCK-mediated phosphorylation. Furthermore, we determine that this novel cascade is switched on or off by physiological stimuli. We propose that RhoA/ROCK/PIIa-mediated regulation of actin stability, shown to be essential for neuritogenesis, may constitute a central mechanism throughout neuronal differentiation.
引用
收藏
页码:1267 / 1279
页数:13
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