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Gene Review

Rho  -  rhodopsin

Mus musculus

Synonyms: L opsin, LWS opsin, Long Wavelength Sensitive opsin, Noerg1, Opn2, ...
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Disease relevance of Rho

  • Recent studies have suggested that the proliferative effects of p21(ras) may depend on signaling outputs from the small Rho GTPases, Rac and Rho, but the physiologic importance of these interactions in an animal disease model has not been established [1].
  • We showed previously that anti-RhoA small interfering RNA (siRNA) inhibited aggressive breast cancer more effectively than conventional blockers of Rho-mediated signaling pathways [2].
  • Subretinal injection of recombinant adeno-associated virus (AAV) encoding a Prph2 transgene results in stable generation of outer segment structures and formation of new stacks of discs containing both perpherin-2 and rhodopsin, which in many cases are morphologically similar to normal outer segments [3].
  • Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice [4].
  • Here we report a novel signaling pathway activated by the Rho proteins that may be responsible for their biological activities, including cytoskeleton organization, transformation, apoptosis, and metastasis [5].

Psychiatry related information on Rho


High impact information on Rho

  • Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases [10].
  • Although the underlying mechanism is likely complex, we show that p120 affects NFkB activation and immune homeostasis in part through regulation of Rho GTPases [11].
  • Snails, Swiss, and serum: the solution for Rac 'n' Rho [12].
  • The activation state of Rho following IGF-1 signaling is determined by the tyrosine-phosphorylation status of p190-B RhoGAP and its resulting subcellular relocalization [13].
  • In vitro, activation of Rho-kinase by Rho inhibits adipogenesis and is required for myogenesis [13].

Chemical compound and disease context of Rho


Biological context of Rho


Anatomical context of Rho


Associations of Rho with chemical compounds

  • Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis [19].
  • Vav proteins are Rho family guanine nucleotide exchange factors that become tyrosine phosphorylated in response to adhesion [24].
  • The activation of JNK by Galpha12Q229L was inhibited by dominant-negative RhoA(T19N), and botulinum C3 exoenzyme which specifically inactivates Rho [28].
  • Ablation of RPE65 in Nrl(-/-) and Rho(-/-) mice led to the absence of 11-cis retinal, but increased the total retinoid content, with retinyl esters representing the most abundant retinoid species [29].
  • A single nucleotide transition from G to A was found in the Rho gene that is predicted to result in a substitution of Tyr for Cys at position 110, in an intradiscal loop [30].

Physical interactions of Rho

  • Furthermore, cells infected during the differentiation procedure with a lentiviral vector expressing green fluorescent protein (GFP) under the control of either the rhodopsin promoter or the interphotoreceptor retinoid-binding protein (IRBP) promoter, expressed GFP [31].
  • Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes [32].
  • Our results show that the DRF proteins couple Rho and Src during signaling and the regulation of actin dynamics [33].
  • The Rho subfamily GTP-binding protein Cdc42 mediates actin cytoskeletal rearrangements and cell cycle progression and is essential for Ras transformation [34].
  • The Rho family of guanosine triphosphate (GTP)-binding proteins regulates cytoskeletal reorganization in all cells tested and Rac and Rho have both been shown to regulate melanocyte dendrite formation [35].

Enzymatic interactions of Rho

  • This is the first demonstration of an endogenous Rho family member being phosphorylated in vivo and indicates that phosphorylation is an important mechanism to control the stability and function of this GTPase-deficient Rho protein [36].

Regulatory relationships of Rho

  • The gene Rpe65 is specifically expressed in the PE and essential for the re-isomerization of all-trans retinol in the visual cycle and thus for the regeneration of rhodopsin after bleaching [37].
  • It acts synergistically with Crx to regulate rhodopsin transcription [38].
  • In vitro and in vivo analyses indicate that Tiam1 activates the Rho like GTPase Rac1 [39].
  • We found that Cdc42 also downregulates Rho activity [40].
  • We observed that the foci of transformed NIH 3T3 cells caused by Mas were similar to those caused by activated Rho and Rac proteins [41].

Other interactions of Rho


Analytical, diagnostic and therapeutic context of Rho


  1. Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. Ingram, D.A., Hiatt, K., King, A.J., Fisher, L., Shivakumar, R., Derstine, C., Wenning, M.J., Diaz, B., Travers, J.B., Hood, A., Marshall, M., Williams, D.A., Clapp, D.W. J. Exp. Med. (2001) [Pubmed]
  2. Intravenous delivery of anti-RhoA small interfering RNA loaded in nanoparticles of chitosan in mice: safety and efficacy in xenografted aggressive breast cancer. Pill??, J.Y., Li, H., Blot, E., Bertrand, J.R., Pritchard, L.L., Opolon, P., Maksimenko, A., Lu, H., Vannier, J.P., Soria, J., Malvy, C., Soria, C. Hum. Gene Ther. (2006) [Pubmed]
  3. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Ali, R.R., Sarra, G.M., Stephens, C., Alwis, M.D., Bainbridge, J.W., Munro, P.M., Fauser, S., Reichel, M.B., Kinnon, C., Hunt, D.M., Bhattacharya, S.S., Thrasher, A.J. Nat. Genet. (2000) [Pubmed]
  4. Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Chang, G.Q., Hao, Y., Wong, F. Neuron (1993) [Pubmed]
  5. Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. Perona, R., Montaner, S., Saniger, L., Sánchez-Pérez, I., Bravo, R., Lacal, J.C. Genes Dev. (1997) [Pubmed]
  6. Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Nishimura, D.Y., Fath, M., Mullins, R.F., Searby, C., Andrews, M., Davis, R., Andorf, J.L., Mykytyn, K., Swiderski, R.E., Yang, B., Carmi, R., Stone, E.M., Sheffield, V.C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. Crosstalk between Rap1 and Rac regulates secretion of sAPPalpha. Maillet, M., Robert, S.J., Cacquevel, M., Gastineau, M., Vivien, D., Bertoglio, J., Zugaza, J.L., Fischmeister, R., Lezoualc'h, F. Nat. Cell Biol. (2003) [Pubmed]
  8. Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network. Faucherre, A., Desbois, P., Satre, V., Lunardi, J., Dorseuil, O., Gacon, G. Hum. Mol. Genet. (2003) [Pubmed]
  9. Expression of Rho-kinase and its functional role in the contractile activity of the mouse vas deferens. Büyükafşar, K., Levent, A., Ark, M. Br. J. Pharmacol. (2003) [Pubmed]
  10. Yersinia virulence depends on mimicry of host rho-family nucleotide dissociation inhibitors. Prehna, G., Ivanov, M.I., Bliska, J.B., Stebbins, C.E. Cell (2006) [Pubmed]
  11. p120-catenin mediates inflammatory responses in the skin. Perez-Moreno, M., Davis, M.A., Wong, E., Pasolli, H.A., Reynolds, A.B., Fuchs, E. Cell (2006) [Pubmed]
  12. Snails, Swiss, and serum: the solution for Rac 'n' Rho. Ridley, A.J., Hall, A. Cell (2004) [Pubmed]
  13. Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Sordella, R., Jiang, W., Chen, G.C., Curto, M., Settleman, J. Cell (2003) [Pubmed]
  14. Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages. Leverrier, Y., Ridley, A.J. Curr. Biol. (2001) [Pubmed]
  15. Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration. Bourguignon, L.Y., Zhu, H., Shao, L., Chen, Y.W. J. Cell Biol. (2000) [Pubmed]
  16. The transcriptional coactivator FHL2 transmits Rho signals from the cell membrane into the nucleus. Müller, J.M., Metzger, E., Greschik, H., Bosserhoff, A.K., Mercep, L., Buettner, R., Schüle, R. EMBO J. (2002) [Pubmed]
  17. Activation of rho through a cross-link with polyamines catalyzed by Bordetella dermonecrotizing toxin. Masuda, M., Betancourt, L., Matsuzawa, T., Kashimoto, T., Takao, T., Shimonishi, Y., Horiguchi, Y. EMBO J. (2000) [Pubmed]
  18. Clostridium novyi alpha-toxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins. Selzer, J., Hofmann, F., Rex, G., Wilm, M., Mann, M., Just, I., Aktories, K. J. Biol. Chem. (1996) [Pubmed]
  19. Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis. Hall, A.B., Gakidis, M.A., Glogauer, M., Wilsbacher, J.L., Gao, S., Swat, W., Brugge, J.S. Immunity (2006) [Pubmed]
  20. Regulation of innate immunity by Rho GTPases. Bokoch, G.M. Trends Cell Biol. (2005) [Pubmed]
  21. Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases. Yamauchi, J., Chan, J.R., Shooter, E.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. Anti-apoptotic function of Rac in hematopoietic cells. Nishida, K., Kaziro, Y., Satoh, T. Oncogene (1999) [Pubmed]
  23. Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line. Cao, Y., Janssen, E.M., Duncan, A.W., Altman, A., Billadeau, D.D., Abraham, R.T. EMBO J. (2002) [Pubmed]
  24. Vav GEFs are required for beta2 integrin-dependent functions of neutrophils. Gakidis, M.A., Cullere, X., Olson, T., Wilsbacher, J.L., Zhang, B., Moores, S.L., Ley, K., Swat, W., Mayadas, T., Brugge, J.S. J. Cell Biol. (2004) [Pubmed]
  25. Differential effect of Rac and Cdc42 on p38 kinase activity and cell cycle progression of nonadherent primary mouse fibroblasts. Philips, A., Roux, P., Coulon, V., Bellanger, J.M., Vié, A., Vignais, M.L., Blanchard, J.M. J. Biol. Chem. (2000) [Pubmed]
  26. 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]
  27. Localization of the rhodopsin gene to the distal half of mouse chromosome 6. Elliott, R.W., Sparkes, R.S., Mohandas, T., Grant, S.G., McGinnis, J.F. Genomics (1990) [Pubmed]
  28. The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Galpha12. Nagao, M., Kaziro, Y., Itoh, H. Oncogene (1999) [Pubmed]
  29. RPE65 Is Essential for the Function of Cone Photoreceptors in NRL-Deficient Mice. Wenzel, A., von Lintig, J., Oberhauser, V., Tanimoto, N., Grimm, C., Seeliger, M.W. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  30. Generation, characterization, and molecular cloning of the Noerg-1 mutation of rhodopsin in the mouse. Pinto, L.H., Vitaterna, M.H., Shimomura, K., Siepka, S.M., McDearmon, E.L., Fenner, D., Lumayag, S.L., Omura, C., Andrews, A.W., Baker, M., Invergo, B.M., Olvera, M.A., Heffron, E., Mullins, R.F., Sheffield, V.C., Stone, E.M., Takahashi, J.S. Vis. Neurosci. (2005) [Pubmed]
  31. High yield of cells committed to the photoreceptor fate from expanded mouse retinal stem cells. Merhi-Soussi, F., Angénieux, B., Canola, K., Kostic, C., Tekaya, M., Hornfeld, D., Arsenijevic, Y. Stem Cells (2006) [Pubmed]
  32. Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. Liang, Y., Fotiadis, D., Filipek, S., Saperstein, D.A., Palczewski, K., Engel, A. J. Biol. Chem. (2003) [Pubmed]
  33. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Tominaga, T., Sahai, E., Chardin, P., McCormick, F., Courtneidge, S.A., Alberts, A.S. Mol. Cell (2000) [Pubmed]
  34. Transformation activity of Cdc42 requires a region unique to Rho-related proteins. Wu, W.J., Lin, R., Cerione, R.A., Manor, D. J. Biol. Chem. (1998) [Pubmed]
  35. The cAMP signaling pathway has opposing effects on Rac and Rho in B16F10 cells: implications for dendrite formation in melanocytic cells. Scott, G., Leopardi, S. Pigment Cell Res. (2003) [Pubmed]
  36. RhoE function is regulated by ROCK I-mediated phosphorylation. Riento, K., Totty, N., Villalonga, P., Garg, R., Guasch, R., Ridley, A.J. EMBO J. (2005) [Pubmed]
  37. Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration. Grimm, C., Wenzel, A., Hafezi, F., Yu, S., Redmond, T.M., Remé, C.E. Nat. Genet. (2000) [Pubmed]
  38. Nrl is required for rod photoreceptor development. Mears, A.J., Kondo, M., Swain, P.K., Takada, Y., Bush, R.A., Saunders, T.L., Sieving, P.A., Swaroop, A. Nat. Genet. (2001) [Pubmed]
  39. Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells. van Leeuwen, F.N., van der Kammen, R.A., Habets, G.G., Collard, J.G. Oncogene (1995) [Pubmed]
  40. Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. Sander, E.E., ten Klooster, J.P., van Delft, S., van der Kammen, R.A., Collard, J.G. J. Cell Biol. (1999) [Pubmed]
  41. Mas oncogene signaling and transformation require the small GTP-binding protein Rac. Zohn, I.E., Symons, M., Chrzanowska-Wodnicka, M., Westwick, J.K., Der, C.J. Mol. Cell. Biol. (1998) [Pubmed]
  42. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Redmond, T.M., Yu, S., Lee, E., Bok, D., Hamasaki, D., Chen, N., Goletz, P., Ma, J.X., Crouch, R.K., Pfeifer, K. Nat. Genet. (1998) [Pubmed]
  43. Regulation of c-myc expression by PDGF through Rho GTPases. Chiariello, M., Marinissen, M.J., Gutkind, J.S. Nat. Cell Biol. (2001) [Pubmed]
  44. Differential requirement for Rho family GTPases in an oncogenic insulin-like growth factor-I receptor-induced cell transformation. Sachdev, P., Jiang, Y.X., Li, W., Miki, T., Maruta, H., Nur-E-Kamal, M.S., Wang, L.H. J. Biol. Chem. (2001) [Pubmed]
  45. Distinct role of phosphatidylinositol 3-kinase and Rho family GTPases in Vav3-induced cell transformation, cell motility, and morphological changes. Sachdev, P., Zeng, L., Wang, L.H. J. Biol. Chem. (2002) [Pubmed]
  46. The role of the RhoA/Rho-kinase signaling pathway in renal vascular reactivity in endothelial nitric oxide synthase null mice. Williams, J., Bogwu, J., Oyekan, A. J. Hypertens. (2006) [Pubmed]
  47. VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Lampugnani, M.G., Zanetti, A., Breviario, F., Balconi, G., Orsenigo, F., Corada, M., Spagnuolo, R., Betson, M., Braga, V., Dejana, E. Mol. Biol. Cell (2002) [Pubmed]
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