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Rho GTPases

Monday 22 September 2003

The Rho GTPases constitue a large family of small GTPases that bind GTP and hydrolyse it to GDP. This is then exchanged for GTP and the cycle is repeated. The switching between these two states regulates a wide range of cellular processes.

Function

Signal transducers mediating growth factor-induced changes to the actin cytoskeleton and activating the phagocyte NADPH oxidase. They have been implicated in numerous cellular processes, from cell migration to cell survival, transcriptional regulation and vesicle trafficking.

In neutrophiles, morphologic polarity is necessary for the motility of mammalian cells. In leukocytes responding to a chemoattractant, this polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). Moreover, in neutrophils, lipid products of PI3Ks appear to regulate activation of Rho GTPases, are required for cell motility and accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. By spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles not only in establishing leukocyte polarity but also as compass molecules that tell the cell where to crawl.

Pathology

- mutation in ARHGEF10 (8p23) in slowed nerve-conduction velocities (NCVs). ARHGEF10 encodes a guanine-nucleotide exchange factor (GEF) for the Rho family of GTPase proteins (RhoGTPases).

Features

- Rho-actin signaling
- Rho GTPase-activating proteins (RhoGAPs)

References

- Piekny A, Werner M, Glotzer M. Cytokinesis: welcome to the Rho zone. Trends Cell Biol. 2005 Dec;15(12):651-8. PMID: 16243528

- Bokoch GM. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 2005 Mar;15(3):163-71. PMID: 15752980

- Ren J, Fang CX. Small guanine nucleotide-binding protein Rho and myocardial function. Acta Pharmacol Sin. 2005 Mar;26(3):279-85. PMID: 15715922

- Walker K, Olson MF. Targeting Ras and Rho GTPases as opportunities for cancer therapeutics. Curr Opin Genet Dev. 2005 Feb;15(1):62-8. PMID: 15661535

- Olson MF. Contraction reaction: mechanical regulation of Rho GTPase. Trends Cell Biol. 2004 Mar;14(3):111-4. PMID: 15055199

- Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol. 2003 Jan;13(1):13-22. PMID: 12480336

- Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer. 2002 Feb;2(2):133-42. PMID: 12635176

- Ridley AJ. Rho family proteins: coordinating cell responses. Trends Cell Biol. 2001 Dec;11(12):471-7. PMID: 11719051

- Luo L. Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci. 2000 Dec;1(3):173-80. PMID: 11257905

- Rickert P, Weiner OD, Wang F, Bourne HR, Servant G. Leukocytes navigate by compass : roles of PI3Kgamma and its lipid products. Trends Cell Biol. 2000 Nov ;10(11):466-73. PMID : 11050418

- Symons M, Settleman J. Rho family GTPases: more than simple switches. Trends Cell Biol. 2000 Oct;10(10):415-9. PMID: 10998597