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Gene Review

Rho1  -  CG8416 gene product from transcript CG8416-RB

Drosophila melanogaster

Synonyms: 19549712, 8416, AAF01186, CG8416, D-Rho1, ...
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Disease relevance of Rho1

  • RhoA and Rac1 gain-of-function and loss-of-function mutants had both disruption of glial cell development and secondary effects on sensory axon fasciculation [1].
  • The DH/PH tandem of PDZ-RhoGEF and C-terminally truncated RhoA were overexpressed in Escherichia coli as TEV protease-cleavable fusion proteins containing GST and a hexahistidine tag at the N-termini, respectively [2].

High impact information on Rho1

  • Indeed, expression of constitutively active forms of Rho1 or Rac1 in adult flies results in ethanol resistance similar to that observed in whir mutants [3].
  • The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation [4].
  • We have identified mutations in the Drosophila homologue of RhoA p21 GTPase, and by analysis of their phenotype show that RhoA is required for the generation of tissue polarity [5].
  • Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates [6].
  • The PKN family of PKC-related protein kinases constitutes the major Rho GTPase-associated protein kinase activities detected in mammalian tissues [7].

Biological context of Rho1

  • Flies harbouring a Rho1 transgene that is specifically expressed in the eye exhibit a dramatic dose dependent disruption of normal eye development [8].
  • Taking advantage of a new probe that allows the visualisation of small RhoGTPase activity in Drosophila, we present evidence that Rho1 is apically activated and essential for epithelial cell invagination, a common morphogenetic movement during embryogenesis [9].
  • Furthermore, the mRNA of RhoGEF64C is also apically enriched, depending on signals present within its open reading frame, suggesting that apical transport of RhoGEF mRNA followed by local translation is a mechanism to spatially restrict Rho1 activity during epithelial cell invagination [9].
  • CONCLUSIONS/SIGNIFICANCE: We conclude that the Rho1 pathway leading to myosin localization to the future cytokinetic furrow is relatively straightforward, where only Rok is needed, and it is only needed to maintain phosphorylation of the myosin RLC [10].
  • In the reciprocal pathway, co-expression of dominant negative Rho-kinase and constitutive active Rho1 induces a Rac1-like phenotype [11].

Anatomical context of Rho1

  • We propose that Rho1, cappuccino and spire are elements of a conserved developmental cassette that is capable of directly mediating crosstalk between microtubules and microfilaments [12].
  • Here we show interactions between Drosophila Rho1 and the adherens junction components alpha-catenin and p120(ctn) [13].
  • In the posterior spiracles of the fly embryo, this asymmetric activation is achieved by at least two mechanisms: the apical enrichment of Rho1; and the opposing distribution of Rho activators and inhibitors to distinct compartments of the cell membrane [9].
  • Co-expression of dominant negative Rho-kinase and constitutive active Rho1 also induces filopodia formation, with Diaphanous enriched at the tips [11].
  • Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1 [14].

Associations of Rho1 with chemical compounds

  • Screening of fungal virulence traits using mutagenized fungi to determine changes in fungal infectivity of non-mammalian hosts has been used to identify novel virulence proteins used to infect C. elegans such as Kin1 (a serine/threonine protein kinase) and Rom2 (a Rho1 guanyl-nucleotide exchange factor) from Cryptococcus neoformans [15].
  • Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase [16].
  • The plakin Short Stop and the RhoA GTPase are required for E-cadherin-dependent apical surface remodeling during tracheal tube fusion [17].
  • Together, these findings indicate a link between Rho-LIMK signaling and steroid hormone-induced gene expression in the context of metamorphosis and thereby establish a novel role for the Rho GTPase in development [18].
  • In both cell types, the inhibition of Rho GTPase activity by microinjecting C3 transferase into the cells resulted in the disassembly of stress fibers and FAs [19].

Physical interactions of Rho1


Regulatory relationships of Rho1


Other interactions of Rho1

  • Reciprocal regulation of Rac1 and Rho1 in Drosophila circulating immune surveillance cells [11].
  • In Drosophila S2 cells, we previously showed that myosin II is recruited to the furrow independently of F-actin, and that Rho1 and Rok are essential for this recruitment [1] [10].
  • Here, we test the function of this cable by live analysis of GFP-actin-expressing embryos in which the cable is disrupted by modulating Rho1 signaling or by loss of non-muscle myosin (Zipper) function [24].
  • The mechanism linking Moesin activity with RhoA function and Hedgehog signalling remains to be elucidated [25].
  • Drosophila RhoGAP68F is a putative GTPase activating protein for RhoA participating in gastrulation [26].

Analytical, diagnostic and therapeutic context of Rho1

  • We demonstrate through the characterization of two alleles of the RhoGAP68F gene that RhoGAP68F participates in gastrulation of the embryo, a morphogenetic event driven by cell constriction that involves RhoA signaling [26].
  • The nucleotide-free DH/PH-RhoA complex was purified by gel filtration and crystallized [2].


  1. RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Sepp, K.J., Auld, V.J. Development (2003) [Pubmed]
  2. Preliminary crystallographic analysis of the complex of the human GTPase RhoA with the DH/PH tandem of PDZ-RhoGEF. Oleksy, A., Barton, H., Devedjiev, Y., Purdy, M., Derewenda, U., Otlewski, J., Derewenda, Z.S. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
  3. Distinct Behavioral Responses to Ethanol Are Regulated by Alternate RhoGAP18B Isoforms. Rothenfluh, A., Threlkeld, R.J., Bainton, R.J., Tsai, L.T., Lasek, A.W., Heberlein, U. Cell (2006) [Pubmed]
  4. The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Barrett, K., Leptin, M., Settleman, J. Cell (1997) [Pubmed]
  5. The role of RhoA in tissue polarity and Frizzled signalling. Strutt, D.I., Weber, U., Mlodzik, M. Nature (1997) [Pubmed]
  6. Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons. Lundström, A., Gallio, M., Englund, C., Steneberg, P., Hemphälä, J., Aspenström, P., Keleman, K., Falileeva, L., Dickson, B.J., Samakovlis, C. Genes Dev. (2004) [Pubmed]
  7. The Drosophila Pkn protein kinase is a Rho/Rac effector target required for dorsal closure during embryogenesis. Lu, Y., Settleman, J. Genes Dev. (1999) [Pubmed]
  8. Characterization of rho GTPase family homologues in Drosophila melanogaster: overexpressing Rho1 in retinal cells causes a late developmental defect. Hariharan, I.K., Hu, K.Q., Asha, H., Quintanilla, A., Ezzell, R.M., Settleman, J. EMBO J. (1995) [Pubmed]
  9. Compartmentalisation of Rho regulators directs cell invagination during tissue morphogenesis. Sim??es, S., Denholm, B., Azevedo, D., Sotillos, S., Martin, P., Skaer, H., Hombr??a, J.C., Jacinto, A. Development (2006) [Pubmed]
  10. Rho Kinase's Role in Myosin Recruitment to the Equatorial Cortex of Mitotic Drosophila S2 Cells Is for Myosin Regulatory Light Chain Phosphorylation. Dean, S.O., Spudich, J.A. PLoS ONE (2006) [Pubmed]
  11. Reciprocal regulation of Rac1 and Rho1 in Drosophila circulating immune surveillance cells. Williams, M.J., Habayeb, M.S., Hultmark, D. J. Cell. Sci. (2007) [Pubmed]
  12. Coordination of microtubule and microfilament dynamics by Drosophila Rho1, Spire and Cappuccino. Rosales-Nieves, A.E., Johndrow, J.E., Keller, L.C., Magie, C.R., Pinto-Santini, D.M., Parkhurst, S.M. Nat. Cell Biol. (2006) [Pubmed]
  13. Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. Magie, C.R., Pinto-Santini, D., Parkhurst, S.M. Development (2002) [Pubmed]
  14. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells. Kunwar, P.S., Starz-Gaiano, M., Bainton, R.J., Heberlein, U., Lehmann, R. PLoS Biol. (2003) [Pubmed]
  15. Using non-mammalian hosts to study fungal virulence and host defense. Fuchs, B.B., Mylonakis, E. Curr. Opin. Microbiol. (2006) [Pubmed]
  16. Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae. Kohno, H., Tanaka, K., Mino, A., Umikawa, M., Imamura, H., Fujiwara, T., Fujita, Y., Hotta, K., Qadota, H., Watanabe, T., Ohya, Y., Takai, Y. EMBO J. (1996) [Pubmed]
  17. The plakin Short Stop and the RhoA GTPase are required for E-cadherin-dependent apical surface remodeling during tracheal tube fusion. Lee, S., Kolodziej, P.A. Development (2002) [Pubmed]
  18. Rho-LIM kinase signaling regulates ecdysone-induced gene expression and morphogenesis during Drosophila metamorphosis. Chen, G.C., Gajowniczek, P., Settleman, J. Curr. Biol. (2004) [Pubmed]
  19. Rho-mediated assembly of stress fibers is differentially regulated in corneal fibroblasts and myofibroblasts. Anderson, S., DiCesare, L., Tan, I., Leung, T., SundarRaj, N. Exp. Cell Res. (2004) [Pubmed]
  20. Plexin B mediates axon guidance in Drosophila by simultaneously inhibiting active Rac and enhancing RhoA signaling. Hu, H., Marton, T.F., Goodman, C.S. Neuron (2001) [Pubmed]
  21. Regulation of rho family GTPases is required to prevent axons from crossing the midline. Fritz, J.L., VanBerkum, M.F. Dev. Biol. (2002) [Pubmed]
  22. Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition. Peterson, F.C., Penkert, R.R., Volkman, B.F., Prehoda, K.E. Mol. Cell (2004) [Pubmed]
  23. Modifiers of muscle and heart cell fate specification identified by gain-of-function screen in Drosophila. Bidet, Y., Jagla, T., Da Ponte, J.P., Dastugue, B., Jagla, K. Mech. Dev. (2003) [Pubmed]
  24. Dynamic analysis of actin cable function during Drosophila dorsal closure. Jacinto, A., Wood, W., Woolner, S., Hiley, C., Turner, L., Wilson, C., Martinez-Arias, A., Martin, P. Curr. Biol. (2002) [Pubmed]
  25. Independent roles of Drosophila Moesin in imaginal disc morphogenesis and hedgehog signalling. Molnar, C., de Celis, J.F. Mech. Dev. (2006) [Pubmed]
  26. Drosophila RhoGAP68F is a putative GTPase activating protein for RhoA participating in gastrulation. Sanny, J., Chui, V., Langmann, C., Pereira, C., Zahedi, B., Harden, N. Dev. Genes Evol. (2006) [Pubmed]
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