RhoGDI: multiple functions in the regulation of Rho family GTPase activities

Athanassios Dovas; John R. Couchman

doi:10.1042/bj20050104

journal article Aug 09, 2005

RhoGDI: multiple functions in the regulation of Rho family GTPase activities

Athanassios Dovas John R. Couchman

Biochemical Journal Vol. 390 No. 1 pp. 1-9 · Portland Press Ltd.

View at Publisher Save 10.1042/bj20050104

Abstract

RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho family GTPases typified by its ability to prevent nucleotide exchange and membrane association. Structural studies on GTPase–RhoGDI complexes, in combination with biochemical and cell biological results, have provided insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association–dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability and the importance of the particular membrane microenvironment that represents the site of action for GTPases. All these results point to a wider role for RhoGDI than initially perceived, making it a binding partner that can tightly control Rho GTPases, but which also allows them to reach their full spectrum of activities.

Topics

No keywords indexed for this article. Browse by subject →

References

80

[1]

Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia

Catherine D Nobes, Alan Hall

Cell 1995 10.1016/0092-8674(95)90370-4

[2]

Rho GTPases in cell biology

Sandrine Etienne-Manneville, Alan Hall

Nature 2002 10.1038/nature01148

[3]

Bishop "RhoGTPases and their effector proteins" Biochem. J. (2000) 10.1042/bj3480241

[4]

Guanine nucleotide exchange factors for Rho GTPases: turning on the switch

Anja Schmidt, Alan Hall

Genes & Development 2002 10.1101/gad.1003302

[5]

Moon "Rho GTPase-activating proteins in cell regulation" Trends Cell Biol. (2003) 10.1016/s0962-8924(02)00004-1

[6]

Sasaki "The Rho small G protein family – RhoGDI system as a temporal and spatial determinant for cytoskeletal control" Biochem. Biophys. Res. Commun. (1998) 10.1006/bbrc.1998.8253

[7]

Olofsson "Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling" Cell. Signal. (1999) 10.1016/s0898-6568(98)00063-1

[8]

Masuda "Molecular cloning and characterisation of yeast rho GDP dissociation inhibitor" J. Biol. Chem. (1994) 10.1016/s0021-9258(17)32079-3

[9]

Yap "Molecular characterisation of the Caenorhabditis elegans Rho GDP-dissociation inhibitor" Eur. J. Biochem. (1999) 10.1046/j.1432-1327.1999.00953.x

[10]

Imai "A Rho GDP-dissociation inhibitor is involved in cytokinesis in Dictyostelium" Biochem. Biophys. Res. Commun. (2002) 10.1016/s0006-291x(02)00861-6

[11]

Rivero "Defects in cytokinesis, actin reorganisation and the contractile vacuole in cells deficient in RhoGDI" EMBO J. (2002) 10.1093/emboj/cdf449

[12]

Bischoff "Localization of AtROP4 and AtROP6 and interaction with the guanine nucleotide dissociation inhibitor AtRhoGDI1 from Arabidopsis" Plant Mol. Biol. (2000) 10.1023/a:1006341210147

[13]

Nancy "The δ subunit of the retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases" J. Biol. Chem. (2002) 10.1074/jbc.m109983200

[14]

Michaelson "Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding" J. Cell Biol. (2001) 10.1083/jcb.152.1.111

[15]

Platko "A single residue can modify target-binding affinity and activity of the functional domain of the Rho-subfamily GDP dissociation inhibitors" Proc. Natl. Acad. Sci. U.S.A. (1995) 10.1073/pnas.92.7.2974

[16]

Gorvel "Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity" FEBS Lett. (1998) 10.1016/s0014-5793(98)00020-9

[17]

RhoGDI-3 Is a New GDP Dissociation Inhibitor (GDI)

Gérard Zalcman, Violaine Closson, Jacques Camonis et al.

Journal of Biological Chemistry 1996 10.1074/jbc.271.48.30366

[18]

RhoGDIγ: A GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas

Chaker N. Adra, Danny Manor, Jon L. Ko et al.

Proceedings of the National Academy of Sciences 1997 10.1073/pnas.94.9.4279

[19]

Togawa "Progressive impairment of kidneys and reproductive organs in mice lacking RhoGDIα" Oncogene (1999) 10.1038/sj.onc.1202921

[20]

Brunet "RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its unique N-terminal domain" Traffic (2002) 10.1034/j.1600-0854.2002.30504.x

[21]

Guillemot "Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from embryonal stem cell differentiation" Blood (1996) 10.1182/blood.v88.7.2722.bloodjournal8872722

[22]

Yin "Immune responses in mice deficient in Ly-GDI, a lymphoid-specific regulator of Rho GTPases" Mol. Immunol. (1997) 10.1016/s0161-5890(97)00053-9

[23]

Koch "Association of the Rho family small GTP-binding proteins with Rho GDP dissociation inhibitor in Saccharomyces cerevisiae" Oncogene (1997) 10.1038/sj.onc.1201194

[24]

Anastasiadis "Inhibition of RhoA by p120 catenin" Nat. Cell Biol. (2000) 10.1038/35023588

[25]

Degani "The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading" J. Cell Biol. (2002) 10.1083/jcb.200108030

[26]

Keep "A modulator of rho family G proteins, rhoGDI, binds these G proteins via an immunoglobulin-like domain and a flexible N-terminal arm" Structure (1997) 10.1016/s0969-2126(97)00218-9

[27]

Gosser "C-terminal binding domain of RhoGDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases" Nature (London) (1997) 10.1038/42961

[28]

Golovanov "Structure-activity relationships in flexible protein domains: Regulation of rho GTPases by RhoGDI and D4 GDI" J. Mol. Biol. (2001) 10.1006/jmbi.2000.4262

[29]

Longenecker "How RhoGDI binds Rho" Acta Crytallogr., Sect. D: Biol. Crystallogr. (1999) 10.1107/s090744499900801x

[30]

Hoffman "Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI" Cell (2000) 10.1016/s0092-8674(00)80670-4

[31]

Grizot "Crystal structure of the Rac1-RhoGDI complex involved in NADPH oxidase activation" Biochemistry (2001) 10.1021/bi010288k

[32]

Schefzek "The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI" Nat. Struct. Biol. (2000) 10.1038/72392

[33]

Residues of the Rho Family GTPases Rho and Cdc42 That Specify Sensitivity to Dbl-like Guanine Nucleotide Exchange Factors

Rong Li, Yi Zheng

Journal of Biological Chemistry 1997 10.1074/jbc.272.8.4671

[34]

Golovanov "Structural consequences of site-directed mutagenesis in flexible protein domains. NMR characterization of the L(55,56)S mutant of RhoGDI" Eur. J. Biochem. (2001) 10.1046/j.1432-1327.2001.02100.x

[35]

Nomanbhoy "Kinetics of Cdc42 membrane extraction by rho-GDI monitored by real-time fluorescence resonance energy transfer" Biochemistry (1999) 10.1021/bi982198u

[36]

Lang "Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes" EMBO J. (1996) 10.1002/j.1460-2075.1996.tb00383.x

[37]

Forget "Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes" Biochem. J. (2002) 10.1042/bj3610243

[38]

Ellerbroek "Serine phosphorylation negatively regulates RhoA in vivo" J. Biol. Chem. (2003) 10.1074/jbc.m213066200

[39]

Tu "Epidermal growth factor-dependent regulation of Cdc42 is mediated by the Src tyrosine kinase" J. Biol. Chem. (2003) 10.1074/jbc.m307021200

[40]

Bourmeyster "Phosphorylation of RhoGDI stabilizes the RhoA-RhoGDI complex in neutrophil cytosol" Biochem. Biophys. Res. Commun. (1996) 10.1006/bbrc.1996.0011

[41]

Unwin "Global effects of BCR/ABL and TEL/PDGFRbeta expression on the proteome and phosphoproteome: Identification of the Rho pathway as a target of BCR/ABL" J. Biol. Chem. (2005) 10.1074/jbc.m410598200

[42]

Mehta "Protein kinase Cα signals Rho-guanine nucleotide dissociation inhibitor phosphorylation and Rho activation and regulates the endothelial cell barrier function" J. Biol. Chem. (2001) 10.1074/jbc.m101927200

[43]

Price "Calcium signalling regulates translocation and activation of Rac" J. Biol. Chem. (2003) 10.1074/jbc.m302083200

[44]

DerMardirossian "Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase" Mol. Cell (2004) 10.1016/j.molcel.2004.05.019

[45]

Bretscher "ERM proteins and Merlin: Integrators at the cell cortex" Nat. Rev. Mol. Cell Biol. (2002) 10.1038/nrm882

[46]

Takahashi "Direct interaction of the Rho GDP dissociation inhibitor with ezrin/radixin/moesin initiates the activation of the Rho small G protein" J. Biol. Chem. (1997) 10.1074/jbc.272.37.23371

[47]

Hirao "Regulation mechanism of ERM (Ezrin/Radixin/Moesin) protein/plasma membrane association: possible involvement of phosphatidylinositol turnover and Rho-dependent signalling pathway" J. Cell Biol. (1996) 10.1083/jcb.135.1.37

[48]

Allenspach "ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse" Immunity (2001) 10.1016/s1074-7613(01)00224-2

[49]

Ota "LyGDI functions in cancer metastasis by anchoring Rho proteins to the cell membrane" Mol. Carcinog. (2004) 10.1002/mc.20006

[50]

Yamashita "The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI" Nat. Neurosci. (2003) 10.1038/nn1045

Showing 50 of 80 references

Cited By

342

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases

Boris Lavanderos, Ian Silva · 2020

Frontiers in Cell and Developmental...

RhoGDI2 positively regulates the Rho GTPases activation in response to the β2 outside-in signaling in T cells adhesion and migration on ICAM-1

Wenai Liu, Xuehao Wang · 2019

Journal of Leukocyte Biology

Rho GDP dissociation inhibitor-mediated disruption of Rho GTPase activity impairs lens fiber cell migration, elongation and survival

Rupalatha Maddala, Lixing W. Reneker · 2008

Developmental Biology

Metrics

342

Citations

80

References

Details

Published: Aug 09, 2005
Vol/Issue: 390(1)
Pages: 1-9

Authors

A

Athanassios Dovas

Division of Biomedical Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, U.K.

J

John R. Couchman

Division of Biomedical Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, U.K.

Cite This Article

Athanassios Dovas, John R. Couchman (2005). RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Biochemical Journal, 390(1), 1-9. https://doi.org/10.1042/bj20050104

RhoGDI: multiple functions in the regulation of Rho family GTPase activities

You May Also Like