Rac1 Regulates Neuronal Polarization through the WAVE Complex

Neuronal migration and axon growth, key events during neuronal development, require distinct changes in the cytoskeleton. Although many molecular regulators of polarity have been identified and characterized, relatively little is known about their physiological role in this process. To study the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1 -deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo and in vitro . In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott–Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1 -knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth.

Rac1 and Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons, Journal of Cell Science

Local changes in microtubule network mobility instruct neuronal polarization and axon specification

Full article: Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses

Cells, Free Full-Text

Development of neuronal polarity in vivo - ScienceDirect

Frontiers Rac1, A Potential Target for Tumor Therapy

Cells, Free Full-Text

Rac1 plays an essential role in axon growth and guidance and in neuronal survival in the central and peripheral nervous systems, Neural Development

Journal of Cellular Physiology, Cell Biology Journal

Rho GTPase signaling in cancer progression and dissemination

STK25 and MST3 Have Overlapping Roles to Regulate Rho GTPases during Cortical Development

Cancers, Free Full-Text

Cells, Free Full-Text

Rac-deficient cerebellar granule neurons die before they migrate to the internal granule layer