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MBC in Press, published online ahead of print March 8, 2006
Mol. Biol. Cell 10.1091/mbc.E05-08-0753

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Submitted on August 12, 2005
Revised on February 22, 2006
Accepted on February 24, 2006

Rac3-induced Neuritogenesis Requires Binding to Neurabin I

Donata Orioli,* Ivan N. Colaluca,*{dagger} Miria Stefanini,* Silvano Riva,* Carlos G. Dotti,{ddagger} and Fiorenzo A. Peverali*

*Istituto di Genetica Molecolare, C.N.R., I-27100 Pavia, Italy; {ddagger}Department of Human Genetics and Flanders Institute of Biotechnology (VIB4), Catholic University of Leuven, 3000-Leuven, Belgium

Monitoring Editor: Marianne Bronner-Fraser

Rac3, a neuronal GTP-binding protein of the Rho family, induces neuritogenesis in primary neurons. Using yeast two hybrid analysis we show that Neurabin I, the neuronal F-actin binding protein, is a direct Rac3 interacting molecule. Biochemical and light microscopy studies indicate that Neurabin I copartitions and colocalizes with Rac3 at the growth cones of neurites, inducing Neurabin I association to the cytoskeleton. Moreover, Neurabin-I anti-sense oligonucleotides abolish Rac3-induced neuritogenesis, which in turn is rescued by exogenous Neurabin-I but not by Neurabin-I mutant lacking the Rac3-binding-domain. These results show that Neurabin-I mediates Rac3-induced neuritogenesis, possibly by anchoring Rac3 to growth cone F-actin.

{dagger}Present address: Istituto Oncologico Europeo, via Ripamonti 435, 20141 Milano, Italy.

Address correspondence to: Donata Orioli (orioli{at}igm.cnr.it)




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