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Originally published as MBC in Press, 10.1091/mbc.E05-08-0753 on March 8, 2006

Vol. 17, Issue 5, 2391-2400, May 2006

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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, Consiglio Nazionale delle Ricerche, I-27100 Pavia, Italy; {ddagger} Department of Human Genetics and Flanders Institute of Biotechnology (VIB4), Catholic University of Leuven, 3000-Leuven, Belgium

Submitted August 12, 2005; Revised February 22, 2006; Accepted February 24, 2006
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 antisense 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.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-08-0753) on March 8, 2006.

Abbreviations used: NB, neuroblastoma; PDZ, PSD-95, DlgA, ZO-1-like domain; PON, phosphorothioate oligonucleotide; RA, retinoic acid.

{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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