Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration
Open Access
- 7 October 2014
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cellular Neuroscience
- Vol. 8, 314
- https://doi.org/10.3389/fncel.2014.00314
Abstract
The Rho family of GTPases belongs to the Ras superfamily of low molecular weight (~21 kDa) guanine nucleotide binding proteins. The most extensively studied members are RhoA, Rac1, and Cdc42. In the last few decades, studies have demonstrated that Rho family GTPases are important regulatory molecules that link surface receptors to the organization of the actin and microtubule cytoskeletons. Indeed, Rho GTPases mediate many diverse critical cellular processes, such as gene transcription, cell-cell adhesion, and cell cycle progression. However, Rho GTPases also play an essential role in regulating neuronal morphology. In particular, Rho GTPases regulate dendritic arborization, spine morphogenesis, growth cone development, and axon guidance. In addition, more recent efforts have underscored an important function for Rho GTPases in regulating neuronal survival and death. Interestingly, Rho GTPases can exert either a pro-survival or pro-death signal in neurons depending upon both the cell type and neurotoxic insult involved. This review summarizes key findings delineating the involvement of Rho GTPases and their effectors in the regulation of neuronal survival and death. Collectively, these results suggest that dysregulation of Rho family GTPases may potentially underscore the etiology of some forms of neurodegenerative disease such as amyotrophic lateral sclerosis (ALS).Keywords
This publication has 129 references indexed in Scilit:
- ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivoScientific Reports, 2012
- Signal Transducer and Activator of Transcription-5 Mediates Neuronal Apoptosis Induced by Inhibition of Rac GTPase ActivityJournal of Biological Chemistry, 2012
- Rotenone activates phagocyte NADPH oxidase by binding to its membrane subunit gp91phoxFree Radical Biology & Medicine, 2012
- Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)Published by Elsevier BV ,2011
- Rac1 Protein Rescues Neurite Retraction Caused by G2019S Leucine-rich Repeat Kinase 2 (LRRK2)Journal of Biological Chemistry, 2011
- Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferationProceedings of the National Academy of Sciences of the United States of America, 2011
- The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrainDevelopmental Neurobiology, 2010
- Targeting a Dominant Negative Rho Kinase to Neurons Promotes Axonal Outgrowth and Partial Functional Recovery After Rat Rubrospinal Tract LesionMolecular Therapy, 2009
- The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis miceProceedings of the National Academy of Sciences of the United States of America, 2006
- GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factorsNature Reviews Molecular Cell Biology, 2005