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The Journal of Neuroscience, February 1, 2006, 26(5):1418-1428; doi:10.1523/JNEUROSCI.4209-05.2006

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Development/Plasticity/Repair
Rac1 and RhoA Promote Neurite Outgrowth through Formation and Stabilization of Growth Cone Point Contacts

Stephanie Woo and Timothy M. Gomez

Department of Anatomy and Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706

Correspondence should be addressed to Dr. Timothy M. Gomez, University of Wisconsin, 257 Bardeen Labs, 1300 University Avenue, Madison, WI 53706. Email: tmgomez{at}wisc.edu

Growth cone advance depends on coordinated membrane protrusion and adhesion to the extracellular matrix. Although many studies have addressed the mechanisms responsible for membrane protrusion, the assembly of integrin-dependent adhesion sites known as point contacts remains poorly understood in growth cones. We show balanced Rac1 activity controls both leading edge protrusion and point contact dynamics during neurite outgrowth. Immunocytochemistry and live imaging of paxillin–green fluorescent protein (GFP) showed that inhibiting Rac1 blocked point contact formation, whereas Rac1 overactivation produced small, unstable point contacts. Both inhibition and overactivation of Rac1 reduced the persistence of lamellar protrusions and neurite outgrowth. Inhibition of ROCK (Rho kinase), a RhoA effector, perturbed protrusion and point contact dynamics similar to Rac1 overactivation. Moreover, the repulsive guidance cue Semaphorin 3A, which signals through Rac1, destabilizes point contacts. Together, our data suggest that coordinated Rho GTPase activities regulate neurite outgrowth through point contact formation and stabilization of membrane protrusion.

Key words: axon pathfinding; integrin; Rho GTPase; Semaphorin 3A; Xenopus; paxillin

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Received Oct. 3, 2005; revised Dec. 15, 2005; accepted Dec. 18, 2005.

Correspondence should be addressed to Dr. Timothy M. Gomez, University of Wisconsin, 257 Bardeen Labs, 1300 University Avenue, Madison, WI 53706. Email: tmgomez{at}wisc.edu

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