Functions of Rac GTPases during Neuronal Development

Abstract

The small GTPases of the Rho family are important regulators of the actin cytoskeleton and are critical for several aspects of neuronal development including the establishment of neuronal polarity, extension of axon and dendrites, neurite branching, axonal navigation and synapse formation. The aim of this review is to present evidence supporting the function of Rac and Rac-related proteins in different aspects of neuronal maturation, based on work performed with organisms including nematodes, Drosophila, Xenopus and mice, and with primary cultures of developing neurons. Three of the 4 vertebrate Rac-related genes, namely Rac1, Rac3 and RhoG, are expressed in the nervous system, and several data support an essential role of all 3 GTPases in distinct aspects of neuronal development and function. Two important points emerge from the analysis presented: highly homologous Rac-related proteins may perform different functions in the developing nervous system; on the other hand, the data also indicate that similar GTPases may perform redundant functions in vivo.

Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases inCaenorhabditis elegansGABAergic Neurotransmission

“…Furthermore, Rac GTPases are regulated by a number of other proteins, which are not simply limited to GEFs and GTPase-activating proteins (GAPs) (de Curtis 2008). To determine which, if any, known C. elegans Rac regulators modulate neuronal synchrony, we exposed an array of Rac regulator mutants to PTZ.…”

“…Rho family GTPases, including Racs, may be differentially regulated in space and time to confer cellular identity (de Curtis 2008). Indeed, disparate Racsignaling pathways have been implicated in several C. elegans developmental processes (Lundquist et al 2001).…”

TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway

“…PIP5KI catalyzes the formation of phosphatidylinositol 4,5-bisphosphate, which acts as a negative regulator of neurite elongation by promoting microtubule depolymerization (31). Rac1 plays a crucial role in several aspects of neural development including neuronal migration, axon formation, and neural progenitor proliferation and survival by coordinating both actin and microtubule remodeling (32,33). However, although a direct role for ARF6 in neuronal migration and cortical layering has not yet been reported, we find that the fine-tuning of ARF6 activity by TBC1D24 is important for radial migration.…”

Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling

“…In non-neuronal cells, Rac1 is known to promote the growth of lamellipodia (Ridley et al, 1992) and, in some cases, formation of neurite-like processes (Kozma et al, 1997;Miyashita et al, 2004). In neurons, Rac1 is involved in the formation, maintenance and structural plasticity of dendritic spines, as well as in the outgrowth of axons (de Curtis, 2008;Luo, 2002;Penzes et al, 2001a;Penzes et al, 2001b;. Hence, we hypothesized that the effects of RILPL2 on cell morphology might be due, at least in part, to the activation of Rac1.…”

“…In neurons, Rho GTPases play a pivotal role in various developmental and maintenance processes, including cell migration, cell polarity, axon growth and guidance, dendrite elaboration and maintenance, as well as in the formation and plasticity of dendritic spines and synapses (Arimura and Kaibuchi, 2007;Linseman and Loucks, 2008;Luo, 2002;Newey et al, 2005;Tada and Sheng, 2006). A growing body of evidence indicates that Rac is particularly crucial for the formation, maintenance and structural plasticity of the dendritic spine (de Curtis, 2008;. For instance, overexpression of Rac in young dissociated hippocampal neurons is sufficient to induce the formation of spines (Wiens et al, 2005), whereas expression of a dominant-negative (DN) Rac in rat hippocampal slices results in a progressive elimination of dendritic spines .…”