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Gene Review

Rac1  -  CG2248 gene product from transcript CG2248-RB

Drosophila melanogaster

Synonyms: 2248, CG2248, D-Rac, D-Rac 1, D-Rac1, ...
 
 
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Disease relevance of Rac1

 

High impact information on Rac1

 

Biological context of Rac1

 

Anatomical context of Rac1

  • A hair begins as a single membrane outgrowth from each wing epithelial cell, and its distal orientation is determined by the restriction of outgrowth to a single distal site on the cell circumference (Wong, L., and P. Adler. 1993. J. Cell Biol. 123:209-211.). We have examined the roles of Cdc42 and Rac1 in the formation of wing hairs [12].
  • CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium [13].
  • Finally, though dominant negative Rac1 is able to block filopodia formation in the overexpression experiments, only Rac2 is necessary for filopodia formed by hemocytes after parasitization [14].
  • The Rac1-like phenotypes, and filopodia formation, could be blocked by co-expression of dominant negative Rac1 [14].
  • In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP3) at the leading edge [15].
 

Associations of Rac1 with chemical compounds

  • RacD possesses a 50 residue C-terminal extension and RacA a 400 residue C-terminal extension that contains a proline-rich region, two BTB domains and a novel C-terminal domain [16].
 

Physical interactions of Rac1

  • The Radish protein has recently been reported to bind to Rac1 [Formstecher et al. (2005) Genome Res. 15:376-384], a small GTPase that regulates cytoskeletal rearrangement and influences neuronal and synaptic morphology [17].
 

Regulatory relationships of Rac1

  • In the reciprocal pathway, co-expression of dominant negative Rho-kinase and constitutive active Rho1 induces a Rac1-like phenotype [14].
  • We have made transgenic flies bearing dominant inhibitory (N17DRacA), and wild-type versions of the DRacA cDNA under control of an Hsp70 promoter [18].
  • Here, we report that axon outgrowth defects within specific subsets of motoneurons expressing constitutively active Drosophila Rac1 largely persist even with the addition of an effector-loop mutation to Rac1 that disrupts its ability to bind to p21-activated kinase (Pak) and other Cdc42/Rac1 interactive-binding (CRIB)-motif effector proteins [19].
  • Similar genetic evidence indicates that RacGAP50C inhibits Rac during cytokinesis [20].
  • The observed genetic interactions are consistent with a model in which Rac signaling is activated by Ras and negatively regulated by RnRacGAP during spermatid differentiation [21].
 

Other interactions of Rac1

  • Cdc42 and Rac1 are members of the rho family of small guanosinetriphosphatases and are required for a diverse set of cytoskeleton-membrane interactions in different cell types [13].
  • These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect [22].
  • To further elucidate this interaction we examined the activities of Rac1 and Rho1 in Drosophila cellular immune surveillance cells [14].
  • These results are consistent with Cdi being a specific downstream target of Rac1 [7].
  • Conversely, blocking Rac activity, either by loss-of-function mutations or expression of dominant negative Rac1, disables the assembly of both actin cable and protrusions by epithelial cells [8].

References

  1. RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Sepp, K.J., Auld, V.J. Development (2003) [Pubmed]
  2. 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]
  3. A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Geisbrecht, E.R., Montell, D.J. Cell (2004) [Pubmed]
  4. Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Hing, H., Xiao, J., Harden, N., Lim, L., Zipursky, S.L. Cell (1999) [Pubmed]
  5. Rescue of photoreceptor degeneration in rhodopsin-null Drosophila mutants by activated Rac1. Chang, H.Y., Ready, D.F. Science (2000) [Pubmed]
  6. Cell biology. Actin' up with Rac1. Colley, N.J. Science (2000) [Pubmed]
  7. A screen for modifiers of RacGAP(84C) gain-of-function in the Drosophila eye revealed the LIM kinase Cdi/TESK1 as a downstream effector of Rac1 during spermatogenesis. Raymond, K., Bergeret, E., Avet-Rochex, A., Griffin-Shea, R., Fauvarque, M.O. J. Cell. Sci. (2004) [Pubmed]
  8. The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure. Woolner, S., Jacinto, A., Martin, P. Dev. Biol. (2005) [Pubmed]
  9. Distinct functions of Rac1 and Cdc42 during axon guidance and growth cone morphogenesis in Drosophila. Matsuura, R., Tanaka, H., Go, M.J. Eur. J. Neurosci. (2004) [Pubmed]
  10. A Drosophila homolog of the Rac- and Cdc42-activated serine/threonine kinase PAK is a potential focal adhesion and focal complex protein that colocalizes with dynamic actin structures. Harden, N., Lee, J., Loh, H.Y., Ong, Y.M., Tan, I., Leung, T., Manser, E., Lim, L. Mol. Cell. Biol. (1996) [Pubmed]
  11. Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila. Chihara, T., Kato, K., Taniguchi, M., Ng, J., Hayashi, S. Development (2003) [Pubmed]
  12. Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. Eaton, S., Wepf, R., Simons, K. J. Cell Biol. (1996) [Pubmed]
  13. CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium. Eaton, S., Auvinen, P., Luo, L., Jan, Y.N., Simons, K. J. Cell Biol. (1995) [Pubmed]
  14. 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]
  15. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. Kunisaki, Y., Nishikimi, A., Tanaka, Y., Takii, R., Noda, M., Inayoshi, A., Watanabe, K., Sanematsu, F., Sasazuki, T., Sasaki, T., Fukui, Y. J. Cell Biol. (2006) [Pubmed]
  16. The Dictyostelium discoideum family of Rho-related proteins. Rivero, F., Dislich, H., Glöckner, G., Noegel, A.A. Nucleic Acids Res. (2001) [Pubmed]
  17. The Drosophila radish gene encodes a protein required for anesthesia-resistant memory. Folkers, E., Waddell, S., Quinn, W.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  18. A dominant inhibitory version of the small GTP-binding protein Rac disrupts cytoskeletal structures and inhibits developmental cell shape changes in Drosophila. Harden, N., Loh, H.Y., Chia, W., Lim, L. Development (1995) [Pubmed]
  19. Isolation of Rho GTPase effector pathways during axon development. Kim, M.D., Kamiyama, D., Kolodziej, P., Hing, H., Chiba, A. Dev. Biol. (2003) [Pubmed]
  20. Mutations in sticky lead to defective organization of the contractile ring during cytokinesis and are enhanced by Rho and suppressed by Rac. D'Avino, P.P., Savoian, M.S., Glover, D.M. J. Cell Biol. (2004) [Pubmed]
  21. RotundRacGAP functions with Ras during spermatogenesis and retinal differentiation in Drosophila melanogaster. Bergeret, E., Pignot-Paintrand, I., Guichard, A., Raymond, K., Fauvarque, M.O., Cazemajor, M., Griffin-Shea, R. Mol. Cell. Biol. (2001) [Pubmed]
  22. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Lee, A., Li, W., Xu, K., Bogert, B.A., Su, K., Gao, F.B. Development (2003) [Pubmed]
 
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