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Published 29 September 2003. doi:10.1083/jcb.200304021
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© The Rockefeller University Press, 0021-9525/2003/9/1267 $5.00
The Journal of Cell Biology, Volume 162, Number 7, 1267-1279

Article

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



Jorge Santos Da Silva1, Miguel Medina1, Cecilia Zuliani2, Alessia Di Nardo3, Walter Witke3 and Carlos G. Dotti1

1 Cavalieri Ottolenghi Scientific Institute, University of Turin, 10043 Orbassano, Torino, Italy
2 Tumour Immunology Programme, German Cancer Research Centre, 69120 Heidelberg, Germany
3 European Moleular Biology Laboratory, Mouse Biology Programme, 00016 Monterotondo, Italy

Address correspondence to Carlos G. Dotti, Cavalieri Ottolenghi Scientific Institute, University of Turin, via Regione Gonzole 10, 10043 Orbassano, Torino, Italy. Tel.: 390116708180. Fax.: 390116708149. email: carlos.dotti{at}unito.it

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.

Key Words: neuronal differentiation; hippocampal neurons; actin dynamics; Rho GTPases; actin-binding proteins

Abbreviations used in this paper: BDNF, brain-derived neurotrophic factor; HA-C3, HA-tagged Rho inhibitory toxin C3; NT-3, neurotrophin 3.


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