Skip to main content
SpringerLink
Log in

Signal transduction pathways regulated by Rho GTPases in Dictyostelium

  • Published:
Journal of Muscle Research & Cell Motility Aims and scope Submit manuscript

Abstract

Rho GTPases are ubiquitously expressed across the eukaryotes where they act as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state. Activation enables Rho GTPases to interact with a multitude of effectors that relay upstream signals to cytoskeletal and other components, eliciting rearrangements of the actin cytoskeleton and diverse other cellular responses. In Dictyostelium the Rho family comprises 15 members. Some of them (Rac1a/b/c, RacF1/F2, RacB) are members of the Rac subfamily, and one, RacA, belongs to the RhoBTB subfamily, however the Rho and Cdc42 subfamilies are not represented. Dictyostelium Rho GTPases regulate actin polymerization, cell morphology, endocytosis, cytokinesis, cell polarity and chemotaxis. Guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) modulate the activation/inactivation cycle of the GTPases. In addition, guanine nucleotide-dissociation inhibitors (GDIs) regulate cycling of the GTPases between membranes and cytosol. Members of these three classes of regulatory molecules along with some effectors have been identified in Dictyostelium during the last years and their role in Rho signaling pathways has been investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adachi H, Takahashi Y, Hasebe T, Shirouzu M, Yokoyama S and Sutoh K (1997) Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis. J Cell Biol 137: 891–898.

    Google Scholar 

  • Aravind L and Koonin EV (1999) Fold prediction and evolutionary analysis of the POZ domain: structural and evolutionary relationship with the potassium channel tetramerization domain. J Mol Biol 285: 1353–1361.

    Google Scholar 

  • Bagrodia S and Cerione RA (1999) PAK to the future. Trends Cell Biol 9: 350–351.

    Google Scholar 

  • Bear JE, Rawls JF and Saxe CL (1998) SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development. J Cell Biol 142: 1325–1335.

    Google Scholar 

  • Bishop AL and Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348: 241–255.

    Google Scholar 

  • Bush J, Franek K and Cardelli J (1993) Cloning and characterization of seven novel Dictyostelium discoideum rac-related genes belonging to the rho family of GTPases. Gene 136: 61–68.

    Google Scholar 

  • Chien S, Chung CY, Sukumaran S, Osborne N, Lee S, Ellsworth C, McNally JG and Firtel RA (2000) The Dictyostelium LIM domain-containing protein LIM2 is essential for proper chemotaxis and morphogenesis. Mol Biol Cell 11: 1275–1291.

    Google Scholar 

  • Chimini G and Chavrier P (2000) Function of Rho family proteins in actin dynamics during phagocytosis and engulfment. Nature Cell Biol 2: E191-E196.

    Google Scholar 

  • Chung CY and Firtel RA (1999) PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis. J Cell Biol 147: 559–575.

    Google Scholar 

  • Chung CY, Lee S, Briscoe C, Ellsworth C and Firtel RA (2000) Role of Rac in controlling the actin cytoskeleton and chemotaxis in motile cells. Proc Natl Acad Sci USA 97: 5225–5230.

    Google Scholar 

  • Chung CY, Potikyan G and Firtel RA (2001) Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol Cell 7: 937–947.

    Google Scholar 

  • Dan I, Watanabe NM and Kusumi A (2001) The Ste20 group kinases as regulators of MAP kinase cascades. Trends Cell Biol 11: 220–230.

    Google Scholar 

  • de la Roche MA and Côté GP (2001) Regulation of Dictyostelium myosin I and II. Biochim Biophys Acta 1525: 245–261.

    Google Scholar 

  • Dumontier M, Höcht P, Mintert U and Faix J (2000) Rac1 GTPases control filopodia formation, cell motility, endocytosis, cytokinesis and development in Dictyostelium. J Cell Sci 113: 2253–2265.

    Google Scholar 

  • Eden S, Rohatgi R, Podtelejnikov AV, Mann M and Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418: 790–793.

    Google Scholar 

  • Eichinger L, Bähler M, Dietz M, Eckerskorn C and Schleicher M (1998) Characterization and cloning of a Dictyostelium Ste20-like protein kinase that phosphorylates the actin-binding protein severin. J Biol Chem 273: 12,952–12,959.

    Google Scholar 

  • Ellis S and Mellor H (2000) Regulation of endocytic tra.c by Rho family GTPases. Trends Cell Biol 10: 85–88.

    Google Scholar 

  • Faix J and Dittrich W (1996) DGAP1, a homologue of rasGTPase activating proteins that controls growth, cytokinesis, and development in Dictyostelium discoideum. FEBS Lett 394: 251–257.

    Google Scholar 

  • Faix J, Clougherty C, Konzok A, Mintert U, Murphy J, Albrecht R, Mühlbauer B and Kuhlman J (1998) The IQGAP-related protein DGAP1 interacts with Rac and is involved in the modulation of the F-actin cytoskeleton and control of cell motility. J Cell Sci 111: 3059–3071.

    Google Scholar 

  • Faix J, Weber I, Mintert U, Köhler J, Lottspeich F and Marriott G (2001) Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and IQGAP-related proteins. EMBO J 20: 3705–3715.

    Google Scholar 

  • Firtel RA and Chung CY (2000) The molecular genetics of chemotaxis: sensing and responding to chemoattractant gradients. BioEssays 22: 603–615.

    Google Scholar 

  • Geissler HA, Ullmann R and Soldati T (2000) The tail domain of myosin M catalyses nucleotide exchange on Rac1 GTPases and can induce actin-driven surface protrusions. Traffic 1: 399–410.

    Google Scholar 

  • Gerald N, Dai J, Ting-Beall HP and de Lozanne A (1998) A role for Dictyostelium RacE in cortical tension and cleavage furrow progression. J Cell Biol 141: 483–492.

    Google Scholar 

  • Higgs HN and Pollard TD (2001) Regulation of actin filament network formation through Arp2/3 complex: activation by a diverse array of proteins. Annu Rev Biochem 70: 649–676.

    Google Scholar 

  • Hoffman GR and Cerione RA (2000) Flipping the switch: the structural basis for signaling through the CRIB motif. Cell 102: 403–406.

    Google Scholar 

  • Hoffman GR, Nassar N and Cerione RA (2000) Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100: 345–356.

    Google Scholar 

  • Imai K, Kijima T, Noda Y, Sutoh K, Yoda K and Adachi H (2002) A Rho GDP-dissociation inhibitor is involved in cytokinesis in Dictyostelium. Biochem Biophys Res Commun 296: 305–312.

    Google Scholar 

  • Insall R, Müller-Taubenberger A, Machesky L, Köhler J, Simmeth E, Atkinson SJ, Weber I and Gerisch G (2001) Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, cytokinesis, and chemotaxis. Cell Motil Cytoskeleton 50: 115–128.

    Google Scholar 

  • Jung G, Remmert K, Wu X, Volosky JM and Hammer JA (2001) The Dictyostelium CARMIL protein links capping protein and the Arp2/3 complex to type I myosins through their SH3 domains. J Cell Biol 153: 1479–1497.

    Google Scholar 

  • Kaibuchi K, Kuroda S and Amano M (1999) Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 68: 459–486.

    Google Scholar 

  • Khurana T, Khurana B and Noegel AA (2002) LIM proteins: association with the actin cytoskeleton. Protoplasma 219: 1–12.

    Google Scholar 

  • Khurana B, Khurana T, Khaire N and Noegel AA (2002b) Functions of LIM proteins in cell polarity and chemotactic motility. EMBO J 21: 5331–5342.

    Google Scholar 

  • Knetsch MLW, Schäfers N, Horstmann H and Manstein DJ (2001) The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac-and Rab-dependent pathways. EMBO J 20: 1620–1629.

    Google Scholar 

  • Larochelle DA, Vithalani KK and de Lozanne A (1996) A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. Mol Biol Cell 133: 1321–1329.

    Google Scholar 

  • Larochelle DA, Vithalani KK and de Lozanne A (1997) Role of the Dictyostelium racE in cytokinesis: mutational analysis and localization studies by use of green fluorescent protein. Mol Biol Cell 8: 935–944.

    Google Scholar 

  • Lee SF and Côté GP (1995) Purification and characterization of a Dictyostelium protein kinase required for the actin-activated MgATPase activity of Dictyostelium myosin ID. J Biol Chem 270: 11,776–11,782.

    Google Scholar 

  • Lee E and Knecht DA (2001) Cytoskeletal alterations in Dictyostelium induced by expression of human Cdc42. Eur J Cell Biol 80: 399–409.

    Google Scholar 

  • Lee SF, Egelhoff TT, Mahasneh A and Côté GP (1996) Cloning and characterization of a Dictyostelium myosin I heavy chain kinase activated by Cdc42 and Rac. J Biol Chem 271: 27,044–27,048.

    Google Scholar 

  • Lee S, Escalante R and Firtel RA (1997) A Ras GAP is essential for cytokinesis and spatial patterning in Dictyostelium. Development 124: 983–996.

    Google Scholar 

  • Lee SF, Mahasneh A, Roche M de la and Côté GP (1998) Regulation of the p21-activated kinase-related Dictyostelium myosin I heavy chain kinase by autophosphorylation, acidic phospholipids, and Ca2+-calmodulin. J Biol Chem 273: 27,11–27,917.

    Google Scholar 

  • Lippincott J and Li R (1998) Sequential assembly of myosin-II, an IQGAP-like protein, and filamentous actin to a ring structure involved in budding yeast cytokinesis. J Cell Biol 140: 355–366.

    Google Scholar 

  • Ludbrook SB, Eccleston JF and Strom M (1997) Cloning and characterization of a rhoGAP homolog from Dictyostelium discoideum. J Biol Chem 272: 15,682–15,686.

    Google Scholar 

  • Machesky LM (1998) Cytokinesis: IQGAPs find a function. Curr Biol 8: R202-R205.

    Google Scholar 

  • May RC, Caron E, Hall A and Machesky LM (2000) Involvement of the Arp2/3 complex in phagocytosis mediated by FccR or CR3. Nature Cell Biol 4: 246–248.

    Google Scholar 

  • Noegel AA and Schleicher M (2000) The actin cytoskeleton of Dictyostelium: a story told by mutants. J Cell Sci 113: 759–766.

    Google Scholar 

  • Oishi N, Adachi H and Sutoh K (2000) Novel Dictyostelium unconventional myosin, MyoM, has a putative RhoGEF domain. FEBS Lett 474: 16–22.

    Google Scholar 

  • Olofsson B (1999) Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal 11: 545–554.

    Google Scholar 

  • Palmieri SJ, Nebl T, Pope RK, Seastone DJ, Lee E, Hinchcliffe EH, Sludder G, Knecht D, Cardelli J and Luna EJ (2000) Mutant Rac1b expression in Dictyostelium: effects on morphology, growth, endocytosis, development, and the actin cytoskeleton. Cell Motil Cytoskel 46: 285–304.

    Google Scholar 

  • Prassler J, Murr A, Stocker S, Faix J, Murphy J and Marriot G (1998) DdLIM is a cytoskeleton-associated protein involved in the protrusion of lamellipodia in Dictyostelium. Mol Biol Cell 9: 545–559.

    Google Scholar 

  • Prokopenko SN, Saint R and Bellen HJ (2000) Untying the gordian knot of cytokinesis: role of small G proteins and their regulators. J Cell Biol 148: 843–848.

    Google Scholar 

  • Quilliam LA, Rebhun JF and Castro AF (2002) A growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases. Prog Nucleic Acid Res Mol Biol 71: 391–444.

    Google Scholar 

  • Ramos S, Khademi F, Somesh BP and Rivero F (2002) Genomic organization and expression pro.le of the small GTPases of the RhoBTB family in human and mouse. Gene 298: 147–157.

    Google Scholar 

  • Rivero F, Albrecht R, Dislich H, Bracco E, Graciotti L, Bozzaro S and Noegel AA (1998) RacF1, a novel member of the Rho protein family in Dictyostelium discoideum, associates transiently with cell contact areas, macropinosomes and phagosomes. Mol Biol Cell 10: 1205–1219.

    Google Scholar 

  • Rivero F, Dislich H, Glöckner G and Noegel AA (2001) The Dictyostelium family of Rho-related proteins. Nucl Acids Res 29: 1068–1079.

    Google Scholar 

  • Rivero F, Illenberger D, Somesh BP, Dislich H, Adam N and Meyer A-K (2002) Defects in cytokinesis, actin reorganization and the contractile vacuole in cells de.cient in RhoGDI. EMBO J 21: 4539–4549.

    Google Scholar 

  • Rupper A and Cardelli J (2001) Regulation of phagocytosis and endophagosomal trafficking pathways in Dictyostelium discoideum. Biochim Biophys Acta 1525: 205–216.

    Google Scholar 

  • Sakurai M, Adachi H and Sutoh K (2001) Mutational analyses of Dictyostelium IQGAP-related protein GAPA: possible interaction with small GTPases in cytokinesis. Biosci Biotechnol Biochem 65: 1912–1916.

    Google Scholar 

  • Schmidt A and Hall A (2002) Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Devel 16: 1587–1609.

    Google Scholar 

  • Schwarz EC, Geissler H and Soldati T (1999) A potential exhaustive screening strategy reveals two novel divergent myosins in Dictyostelium. Cell Biochem Biophys 30: 413–435.

    Google Scholar 

  • Seastone DJ, Harris E, Temesvari LA, Bear JE, Saxe CL and Cardelli J (2001) The WASP-like protein Scar regulates macropinocytosis, phagocytosis and endosomal membrane flow in Dictyostelium. J Cell Sci 114: 2673–2683.

    Google Scholar 

  • Seastone DJ, Lee E, Bush J, Knecht D and Cardelli J (1998) Overexpression of a novel Rho family GTPase, RacC, induces unusual actin-based structures and positively affects phagocytosis in Dictyostelium discoideum. Mol Biol Cell 9: 2891–2904.

    Google Scholar 

  • Shaulsky G, Escalante R and Loomis WF (1996) Developmental signal transduction pathways uncovered by genetic suppressors. Proc Natl Acad Sci USA 93: 15,260–15,265.

    Google Scholar 

  • Takakura A, Miyoshi J, Ishizaki H, Tanaka M, Togawa A, Nishizawa Y, Yoshida H, Nishikawa S and Takai Y (2000) Involvement of a small GTP-binding protein (G protein) regulator, small G protein GDP dissociation stimulator, in antiapoptotic cell survival signaling. Mol Biol Cell 11: 1875–1886.

    Google Scholar 

  • 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 and Takai Y (1999) Progressive impairment of kidneys and reproductive organs in mice lacking RhoGDIa. Oncogene 18: 5373–5380.

    Google Scholar 

  • Van Aelst L and D'Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11: 2295–2322.

    Google Scholar 

  • Vithalani KK, Parent CA, Thorn EM, Penn M, Larochelle DA, Devreotes PN and de Lozanne A (1998) Identification of darlin, a Dictyostelium protein with armadillo-like repeats that binds to small GTPases and is important for the proper aggregation of developing cells. Mol Biol Cell 9: 3095–3116.

    Google Scholar 

  • Wilkins A and Insall RH (2001) Small GTPases in Dictyostelium. Lessons from a social amoeba. Trends Genet 17: 41–48.

    Google Scholar 

  • Zigmond SH, Joyce M, Borleis J, Bokoch GM and Devreotes PN (1997) Regulation of actin polymerization in cell-free systems by GTPγS and Cdc42. J Cell Biol 138: 363–374.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Biochemie I, Medizinische Fakultät, Universität zu Köln, Joseph-Stelzmann-Strasse 52, 50931, Köln, Germany

    Francisco Rivero & Baggavalli P. Somesh

Authors
  1. Francisco Rivero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baggavalli P. Somesh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rivero, F., Somesh, B.P. Signal transduction pathways regulated by Rho GTPases in Dictyostelium . J Muscle Res Cell Motil 23, 737–749 (2002). https://doi.org/10.1023/A:1024423611223

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024423611223

Keywords

Search

Navigation