Ras-related GTPases and the cytoskeleton

A Hall

Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.

Incorporation of the available data on rac in neutrophils, CDC42 in yeast, and rho in fibroblasts suggests a general model for the function of rho-like GTPase (Figure 1). Conversion of an inactive cytoplasmic rho-related p21GDP/GDI complex to active p21. GTP occurs by inhibition of GAP and/or stimulation of exchange factors in response to cell signals. p21.GTP is then able to interact with its target at the plasma membrane. This could result in a conformational change in the target, enabling it to bind cytosolic protein(s). Alternatively, p21.GTP could be actively involved in transporting cytosolic protein(s) to the target. A GAP protein, perhaps intrinsic to the complex, would stimulate GTP hydrolysis allowing p21.GDP to dissociate. Solubilization of p21GDP by interaction with GDI would complete a cycle. What about the nature of the final complex? The rac-regulated NADPH oxidase complex in neutrophils is currently the best understood and most amenable to further biochemical analysis. Two plasma-membrane bound subunits encode the catalytic function necessary for producing superoxide, but the two cytosolic proteins, p47 and p67, are essential for activity. Why the complexity? Production of superoxide is tightly coordinated with phagocytosis, a membrane process driven by rearrangement of cortical actin. This is not unrelated to the membrane ruffling and macropinocytosis that we observe in fibroblasts microinjected with p21rac. It is tempting to speculate, therefore, that in neutrophils rac is involved not only in promoting the assembly of the NADPH oxidase but also in the coordinate reorganization of cortical actin leading to phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 3, Issue 5, pp. 475-479, 05/01/1992
Copyright © 1992 by The American Society for Cell Biology

This article has been cited by other articles:

				A. Mediero, A. Guzman-Aranguez, A. Crooke, A. Peral, and J. Pintor Corneal Re-epithelialization Stimulated by Diadenosine Polyphosphates Recruits RhoA/ROCK and ERK1/2 Pathways Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4982 - 4992. [Abstract] [Full Text] [PDF]

				Y. C. Smith, S. B. Rasmussen, K. K. Grande, R. M. Conran, and A. D. O'Brien Hemolysin of Uropathogenic Escherichia coli Evokes Extensive Shedding of the Uroepithelium and Hemorrhage in Bladder Tissue within the First 24 Hours after Intraurethral Inoculation of Mice Infect. Immun., July 1, 2008; 76(7): 2978 - 2990. [Abstract] [Full Text] [PDF]

				C. X. Sun, M. A.O. Magalhaes, and M. Glogauer Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor J. Cell Biol., October 22, 2007; 179(2): 239 - 245. [Abstract] [Full Text] [PDF]

				H.-C. Chang, C.-Y. Cho, and W.-C. Hung Silencing of the Metastasis Suppressor RECK by RAS Oncogene Is Mediated by DNA Methyltransferase 3b-Induced Promoter Methylation. Cancer Res., September 1, 2006; 66(17): 8413 - 8420. [Abstract] [Full Text] [PDF]

				Z.-G. Zhang, I. Bothe, F. Hirche, M. Zweers, D. Gullberg, G. Pfitzer, T. Krieg, B. Eckes, and M. Aumailley Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of {alpha}2{beta}1 integrin. J. Cell Sci., May 1, 2006; 119(Pt 9): 1886 - 1895. [Abstract] [Full Text] [PDF]

				M. Iwase, J. Luo, S. Nagaraj, M. Longtine, H. B. Kim, B. K. Haarer, C. Caruso, Z. Tong, J. R. Pringle, and E. Bi Role of a Cdc42p Effector Pathway in Recruitment of the Yeast Septins to the Presumptive Bud Site Mol. Biol. Cell, March 1, 2006; 17(3): 1110 - 1125. [Abstract] [Full Text] [PDF]

				W. Ge, F. He, K. J. Kim, B. Blanchi, V. Coskun, L. Nguyen, X. Wu, J. Zhao, J. I.-T. Heng, K. Martinowich, et al. Coupling of cell migration with neurogenesis by proneural bHLH factors PNAS, January 31, 2006; 103(5): 1319 - 1324. [Abstract] [Full Text] [PDF]

				C. X. Sun, G. P. Downey, F. Zhu, A. L. Y. Koh, H. Thang, and M. Glogauer Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass Blood, December 1, 2004; 104(12): 3758 - 3765. [Abstract] [Full Text] [PDF]

				S. A. K. Harvey, S. C. Anderson, and N. SundarRaj Downstream Effects of ROCK Signaling in Cultured Human Corneal Stromal Cells: Microarray Analysis of Gene Expression Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2168 - 2176. [Abstract] [Full Text] [PDF]

				F. E. Nwariaku, P. Rothenbach, Z. Liu, X. Zhu, R. H. Turnage, and L. S. Terada Rho inhibition decreases TNF-induced endothelial MAPK activation and monolayer permeability J Appl Physiol, November 1, 2003; 95(5): 1889 - 1895. [Abstract] [Full Text] [PDF]

				P. J. Woodring, T. Hunter, and J. Y. J. Wang Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases J. Cell Sci., July 1, 2003; 116(13): 2613 - 2626. [Abstract] [Full Text] [PDF]

				M. Glogauer, C. C. Marchal, F. Zhu, A. Worku, B. E. Clausen, I. Foerster, P. Marks, G. P. Downey, M. Dinauer, and D. J. Kwiatkowski Rac1 Deletion in Mouse Neutrophils Has Selective Effects on Neutrophil Functions J. Immunol., June 1, 2003; 170(11): 5652 - 5657. [Abstract] [Full Text] [PDF]

				S. C. Anderson, C. Stone, L. Tkach, and N. SundarRaj Rho and Rho-Kinase (ROCK) Signaling in Adherens and Gap Junction Assembly in Corneal Epithelium Invest. Ophthalmol. Vis. Sci., April 1, 2002; 43(4): 978 - 986. [Abstract] [Full Text] [PDF]

				S. C. Anderson and N. SundarRaj Regulation of a Rho-Associated Kinase Expression during the Corneal Epithelial Cell Cycle Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 933 - 940. [Abstract] [Full Text]

				M. Mills, K. C. Meysick, and A. D. O'Brien Cytotoxic Necrotizing Factor Type 1 of Uropathogenic Escherichia coli Kills Cultured Human Uroepithelial 5637 Cells by an Apoptotic Mechanism Infect. Immun., October 1, 2000; 68(10): 5869 - 5880. [Abstract] [Full Text] [PDF]

				R. Krall, G. Schmidt, K. Aktories, and J. T. Barbieri Pseudomonas aeruginosa ExoT Is a Rho GTPase-Activating Protein Infect. Immun., October 1, 2000; 68(10): 6066 - 6068. [Abstract] [Full Text] [PDF]

				L.-A. H. Allen, F. R. DeLeo, A. Gallois, S. Toyoshima, K. Suzuki, and W. M. Nauseef Transient Association of the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Subunits p47phox and p67phox With Phagosomes in Neutrophils From Patients With X-Linked Chronic Granulomatous Disease Blood, May 15, 1999; 93(10): 3521 - 3530. [Abstract] [Full Text] [PDF]

				M. C. Gustin, J. Albertyn, M. Alexander, and K. Davenport MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae Microbiol. Mol. Biol. Rev., December 1, 1998; 62(4): 1264 - 1300. [Abstract] [Full Text] [PDF]

				J.-H. Chang, J. C. Pratt, S. Sawasdikosol, R. Kapeller, and S. J. Burakoff The Small GTP-Binding Protein Rho Potentiates AP-1 Transcription in T Cells Mol. Cell. Biol., September 1, 1998; 18(9): 4986 - 4993. [Abstract] [Full Text]

				M. Majumdar, T. M. Seasholtz, D. Goldstein, P. de Lanerolle, and J. H. Brown Requirement for Rho-mediated Myosin Light Chain Phosphorylation in Thrombin-stimulated Cell Rounding and Its Dissociation from Mitogenesis J. Biol. Chem., April 24, 1998; 273(17): 10099 - 10106. [Abstract] [Full Text] [PDF]

				C. E. Bazenet, M. A. Mota, and L. L. Rubin The small GTP-binding protein Cdc42 is required for nerve growth factor withdrawal-induced neuronal death PNAS, March 31, 1998; 95(7): 3984 - 3989. [Abstract] [Full Text] [PDF]

				Le Ma, L. C. Cantley, P. A. Janmey, and M. W. Kirschner Corequirement of Specific Phosphoinositides and Small GTP-binding Protein Cdc42 in Inducing Actin Assembly in Xenopus Egg Extracts J. Cell Biol., March 9, 1998; 140(5): 1125 - 1136. [Abstract] [Full Text] [PDF]

				P. A. Wearsch and C. V. Nicchitta Interaction of Endoplasmic Reticulum Chaperone GRP94 with Peptide Substrates Is Adenine Nucleotide-independent J. Biol. Chem., February 21, 1997; 272(8): 5152 - 5156. [Abstract] [Full Text] [PDF]

				R. D. Rooney, P. T. Tuazon, W. E. Meek, E. J. Carroll Jr., J. J. Hagen, E. L. Gump, C. A. Monnig, T. Lugo, and J. A. Traugh Cleavage Arrest of Early Frog Embryos by the G Protein-activated Protein Kinase PAK I J. Biol. Chem., August 30, 1996; 271(35): 21498 - 21504. [Abstract] [Full Text] [PDF]

				A. Best, S. Ahmed, R. Kozma, and L. Lim The Ras-related GTPase Rac1 Binds Tubulin J. Biol. Chem., February 16, 1996; 271(7): 3756 - 3762. [Abstract] [Full Text] [PDF]

				S. Lowe, S. Wong, and W Hong The mammalian ARF-like protein 1 (Arl1) is associated with the Golgi complex J. Cell Sci., January 1, 1996; 109(1): 209 - 220. [Abstract] [PDF]

				F Cvrckova, C De Virgilio, E Manser, J R Pringle, and K Nasmyth Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast. Genes & Dev., August 1, 1995; 9(15): 1817 - 1830. [Abstract] [PDF]

				D. Dash, M. Aepfelbacher, and W. Siess Integrin [IMAGE][IMAGE][IMAGE][IMAGE]-mediated Translocation of CDC42Hs to the Cytoskeleton in Stimulated Human Platelets J. Biol. Chem., July 21, 1995; 270(29): 17321 - 17326. [Abstract] [Full Text] [PDF]

				A. S. Pollock and H. L. Santiesteban Calbindin Expression in Renal Tubular Epithelial Cells J. Biol. Chem., July 7, 1995; 270(27): 16291 - 16301. [Abstract] [Full Text] [PDF]

				E. Prigmore, S. Ahmed, A. Best, R. Kozma, E. Manser, A. W. Segal, and L. Lim A 68-kDa Kinase and NADPH Oxidase Component p67 Are Targets for Cdc42Hs and Rac1 in Neutrophils J. Biol. Chem., May 5, 1995; 270(18): 10717 - 10722. [Abstract] [Full Text] [PDF]

				E. Clark and J. Brugge Integrins and signal transduction pathways: the road taken Science, April 14, 1995; 268(5208): 233 - 239. [Abstract] [PDF]

				D Diekmann, A Abo, C Johnston, A. Segal, and A Hall Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity Science, July 22, 1994; 265(5171): 531 - 533. [Abstract] [PDF]

				G. Moore, T Ayabe, P. Visconti, R. Schultz, and G. Kopf Roles of heterotrimeric and monomeric G proteins in sperm-induced activation of mouse eggs Development, January 11, 1994; 120(11): 3313 - 3323. [Abstract] [PDF]

				S. Arkett, S. Dixon, and S. Sims Lamellipod extension and K+ current in osteoclasts are regulated by different types of G proteins J. Cell Sci., January 2, 1994; 107(2): 517 - 526. [Abstract] [PDF]