Rac1 Regulates Neuronal Polarization through the WAVE Complex
Por um escritor misterioso
Last updated 21 março 2025

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.
Cortical interneuron development: a role for small Rho GTPases

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

PDF) Rac1 Regulates Neuronal Polarization through the WAVE Complex

The role of small GTPases in neuronal morphogenesis and polarity - Gonzalez‐Billault - 2012 - Cytoskeleton - Wiley Online Library

Full article: Regulation of cell adhesion and migration in cortical neurons

WAVE regulatory complex (WRC). (A) Schematic showing mechanisms by

The WAVE Regulatory Complex Links Diverse Receptors to the Actin Cytoskeleton: Cell

Rac1 Controls the Formation of Midline Commissures and the Competency of Tangential Migration in Ventral Telencephalic Neurons

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