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Gene Review

Arhgdia  -  Rho GDP dissociation inhibitor (GDI) alpha

Mus musculus

Synonyms: 5330430M07Rik, C87222, GDI-1, Gdi-1, Gdi1, ...
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Disease relevance of Arhgdia


High impact information on Arhgdia


Biological context of Arhgdia


Anatomical context of Arhgdia

  • In this study, we report that combined disruption of both the Rho GDIalpha and Rho GDIbeta genes in mice resulted in reduction of marginal zone B cells in the spleen, retention of mature T cells in the thymic medulla, and a marked increase in eosinophil numbers [10].
  • Rho GDIalpha and Rho GDIbeta thus play synergistic roles in lymphocyte migration and development by modulating activation cycle of the Rho proteins in a lymphoid organ-specific manner [10].
  • The Rho GDI (GDP dissociation inhibitor) family, consisting of Rho GDIalpha, -beta, and -gamma, is a regulator that keeps the Rho family members in the cytosol as the GDP-bound inactive form and translocates the GDP-bound form from the membranes to the cytosol after the GTP-bound form accomplishes their functions [1].
  • The mRNA expression patterns of Rho-GDIgamma and Rho-GDIalpha were almost identical in the brain with expression in the developing and mature cerebral cortex, striatum, and hippocampus [11].
  • As a consequence, most Rac1b remains bound to the plasma membrane and is not sequestered by Rho-GDI in the cytoplasm [12].

Associations of Arhgdia with chemical compounds

  • Intracellularly perfused recombinant Rho-GDI (an inhibitor of guanine nucleotide exchange specific for the Rho family) attenuated the inhibition of ICa,V by BK [13].
  • Beta8 integrin binds Rho GDP dissociation inhibitor-1 and activates Rac1 to inhibit mesangial cell myofibroblast differentiation [14].
  • Treatment of cells with a cell-permeable chimeric C3 toxin led to complete localization of modified Rho to the cytosolic fraction based on the complexation of ADP-ribosylated Rho with the guanine-nucleotide dissociation inhibitor-1 (GDI-1) [15].
  • The modified complex turned out to be resistant to phosphatidylinositol 4,5-bisphosphate- and GTPgammaS-induced release of Rho from GDI-1 [15].
  • In vivo stimulation of the NO/PKG signaling by treating rats with sildenafil increased RhoA level and RhoA phosphorylation, and enhanced its association to RhoGDI in the pulmonary artery, whereas opposite effects are induced by chronic inhibition of NO synthesis in N-omega-nitro-L-arginine-treated rats [16].

Physical interactions of Arhgdia

  • An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells [17].
  • Introduction of the RhoGDI binding-defective mutation R66A within a constitutively active Cdc42(F28L) background was accompanied by changes in cell shape and an accumulation of Cdc42 in the Golgi when these cells were compared to those expressing Cdc42(F28L) [18].
  • Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells [19].

Regulatory relationships of Arhgdia

  • These results suggest that the signaling pathways of the Rho family members regulated by Rho GDIalpha play important roles in maintaining the structure and physiological function of at least kidneys and reproductive systems in adult mice [1].
  • In this study, we set out to examine how the regulatory protein RhoGDI influences the cellular responses elicited by activated Cdc42 [18].

Other interactions of Arhgdia

  • When co-transfected with Galpha(13)Q226L, the C-terminal domain of radixin synergistically stimulated the SRE activation; RhoGDI inhibited this effect [20].
  • Coimmunoprecipitation studies of Rac2D57N with RhoGDI alpha and Tiam1 demonstrated increased binding of Rac2D57N to these upstream regulators of Rac signaling relative to the wild type [21].
  • We describe a novel mutant of Rac1, R66E (Arg66-->Glu), that fails to bind RhoGDI [17].
  • In intact cells and in cell lysates, glucosylation leads to a translocation of the majority of RhoA GTPase to the membranes whereas a minor fraction is monomeric in the cytosol without being complexed with the guanine nucleotide dissociation inhibitor (GDI-1) [22].
  • Overexpression of either NF-kappaB inhibitory protein IkappaBalphaDeltaN (a degradation resistant mutant IkappaBalpha) or Rho-GDI blocked the strain-induced proliferation of C2C12 cells [23].

Analytical, diagnostic and therapeutic context of Arhgdia


  1. Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Togawa, A., Miyoshi, J., Ishizaki, H., Tanaka, M., Takakura, A., Nishioka, H., Yoshida, H., Doi, T., Mizoguchi, A., Matsuura, N., Niho, Y., Nishimune, Y., Nishikawa, S., Takai, Y. Oncogene (1999) [Pubmed]
  2. Disruption of Rho signaling results in progressive atrioventricular conduction defects while ventricular function remains preserved. Wei, L., Taffet, G.E., Khoury, D.S., Bo, J., Li, Y., Yatani, A., Delaughter, M.C., Klevitsky, R., Hewett, T.E., Robbins, J., Michael, L.H., Schneider, M.D., Entman, M.L., Schwartz, R.J. FASEB J. (2004) [Pubmed]
  3. Human RhoA/RhoGDI complex expressed in yeast: GTP exchange is sufficient for translocation of RhoA to liposomes. Read, P.W., Liu, X., Longenecker, K., Dipierro, C.G., Walker, L.A., Somlyo, A.V., Somlyo, A.P., Nakamoto, R.K. Protein Sci. (2000) [Pubmed]
  4. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Allenspach, E.J., Cullinan, P., Tong, J., Tang, Q., Tesciuba, A.G., Cannon, J.L., Takahashi, S.M., Morgan, R., Burkhardt, J.K., Sperling, A.I. Immunity (2001) [Pubmed]
  5. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Yamashita, T., Tohyama, M. Nat. Neurosci. (2003) [Pubmed]
  6. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Del Pozo, M.A., Kiosses, W.B., Alderson, N.B., Meller, N., Hahn, K.M., Schwartz, M.A. Nat. Cell Biol. (2002) [Pubmed]
  7. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. Michaelson, D., Silletti, J., Murphy, G., D'Eustachio, P., Rush, M., Philips, M.R. J. Cell Biol. (2001) [Pubmed]
  8. Inhibition of Rho family GTPases by Rho GDP dissociation inhibitor disrupts cardiac morphogenesis and inhibits cardiomyocyte proliferation. Wei, L., Imanaka-Yoshida, K., Wang, L., Zhan, S., Schneider, M.D., DeMayo, F.J., Schwartz, R.J. Development (2002) [Pubmed]
  9. 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. Unwin, R.D., Sternberg, D.W., Lu, Y., Pierce, A., Gilliland, D.G., Whetton, A.D. J. Biol. Chem. (2005) [Pubmed]
  10. Defective Chemokine-Directed Lymphocyte Migration and Development in the Absence of Rho Guanosine Diphosphate-Dissociation Inhibitors {alpha} and beta. Ishizaki, H., Togawa, A., Tanaka-Okamoto, M., Hori, K., Nishimura, M., Hamaguchi, A., Imai, T., Takai, Y., Miyoshi, J. J. Immunol. (2006) [Pubmed]
  11. Characterization of Rho-GDIgamma and Rho-GDIalpha mRNA in the developing and mature brain with an analysis of mice with targeted deletions of Rho-GDIgamma. Ferland, R.J., Li, X., Buhlmann, J.E., Bu, X., Walsh, C.A., Lim, B. Brain Res. (2005) [Pubmed]
  12. Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling. Matos, P., Collard, J.G., Jordan, P. J. Biol. Chem. (2003) [Pubmed]
  13. The monomeric G-proteins Rac1 and/or Cdc42 are required for the inhibition of voltage-dependent calcium current by bradykinin. Wilk-Blaszczak, M.A., Singer, W.D., Quill, T., Miller, B., Frost, J.A., Sternweis, P.C., Belardetti, F. J. Neurosci. (1997) [Pubmed]
  14. Beta8 integrin binds Rho GDP dissociation inhibitor-1 and activates Rac1 to inhibit mesangial cell myofibroblast differentiation. Lakhe-Reddy, S., Khan, S., Konieczkowski, M., Jarad, G., Wu, K.L., Reichardt, L.F., Takai, Y., Bruggeman, L.A., Wang, B., Sedor, J.R., Schelling, J.R. J. Biol. Chem. (2006) [Pubmed]
  15. Entrapment of Rho ADP-ribosylated by Clostridium botulinum C3 exoenzyme in the Rho-guanine nucleotide dissociation inhibitor-1 complex. Genth, H., Gerhard, R., Maeda, A., Amano, M., Kaibuchi, K., Aktories, K., Just, I. J. Biol. Chem. (2003) [Pubmed]
  16. Phosphorylation of serine 188 protects RhoA from ubiquitin/proteasome-mediated degradation in vascular smooth muscle cells. Rolli-Derkinderen, M., Sauzeau, V., Boyer, L., Lemichez, E., Baron, C., Henrion, D., Loirand, G., Pacaud, P. Circ. Res. (2005) [Pubmed]
  17. An activating mutant of Rac1 that fails to interact with Rho GDP-dissociation inhibitor stimulates membrane ruffling in mammalian cells. Gandhi, P.N., Gibson, R.M., Tong, X., Miyoshi, J., Takai, Y., Konieczkowski, M., Sedor, J.R., Wilson-Delfosse, A.L. Biochem. J. (2004) [Pubmed]
  18. RhoGDI is required for Cdc42-mediated cellular transformation. Lin, Q., Fuji, R.N., Yang, W., Cerione, R.A. Curr. Biol. (2003) [Pubmed]
  19. Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases. Michaelson, D., Ali, W., Chiu, V.K., Bergo, M., Silletti, J., Wright, L., Young, S.G., Philips, M. Mol. Biol. Cell (2005) [Pubmed]
  20. Radixin stimulates Rac1 and Ca2+/calmodulin-dependent kinase, CaMKII: cross-talk with Galpha13 signaling. Liu, G., Voyno-Yasenetskaya, T.A. J. Biol. Chem. (2005) [Pubmed]
  21. Rac2D57N, a dominant inhibitory Rac2 mutant that inhibits p38 kinase signaling and prevents surface ruffling in bone-marrow-derived macrophages. Abell, A.N., DeCathelineau, A.M., Weed, S.A., Ambruso, D.R., Riches, D.W., Johnson, G.L. J. Cell. Sci. (2004) [Pubmed]
  22. Monoglucosylation of RhoA at threonine 37 blocks cytosol-membrane cycling. Genth, H., Aktories, K., Just, I. J. Biol. Chem. (1999) [Pubmed]
  23. Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal adhesion kinase, Rac-1 GTPase, and NF-kappaB transcription factor. Kumar, A., Murphy, R., Robinson, P., Wei, L., Boriek, A.M. FASEB J. (2004) [Pubmed]
  24. A single residue can modify target-binding affinity and activity of the functional domain of the Rho-subfamily GDP dissociation inhibitors. Platko, J.V., Leonard, D.A., Adra, C.N., Shaw, R.J., Cerione, R.A., Lim, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
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