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The actin-bundling protein cortexillin is the downstream target of a Rac1-signaling pathway required for cytokinesis

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Abstract

During the process of cytokinesis by which eukaryotic cells constrict and divide in two, multiple cellular activities have to be precisely coordinated in space and time to guarantee equal distribution of chromosomes and cytoplasm to the emerging daughter cells. Eventually, constriction of the cleavage furrow leads to the complete separation of the daughter cells. Since the basic observation of cell division some 100 years ago, the principal challenge has been to unravel the detailed molecular mechanisms and signaling events leading to cytokinesis. Regulation of this fundamental cellular process is still poorly understood yet a central issue in modern cell biology. In the recent past it became evident that small GTPases of the Ras super family play a major role during this process. This review is focused on a Rho family GTPase-mediated signaling pathway that is required for cleavage furrow assembly and cytokinesis by the actin-bundling protein cortexillin of D. discoideum cells.

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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 

  • Aspenstrom P (1999) The Rho GTPases have multiple effects on the actin cytoskeleton. Exp Cell Res 246: 20–25.

    Google Scholar 

  • Bi E, Maddox P, Lew DJ, Salmon ED, McMillan JN, Yeh E and Pringle JR (1998) Involvement of an actomyosin contractile ring in Saccharomyces cerevisiae cytokinesis. J Cell Biol 142: 1301–1312.

    Google Scholar 

  • Brill S, Li S, Lyman CW, Church DM, Wasmuth JJ, Weissbach L, Bernards A and Snijders AJ (1996) The Ras GTPase-activatingprotein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Mol Cell Biol 16: 4869–4878.

    Google Scholar 

  • Burkhard P, Steinmetz MO, Schulthess T, Landwehr R, Aebi U and Kammerer RA (1998) Crystallization and preliminary X-ray diffraction analysis of the 190-A-long coiled-coil dimerization domain of the actin-bundling protein cortexillin I from Dictyostelium discoideum. J Struct Biol 122: 293–296.

    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 

  • DeLozanne A and Spudich JA (1987) Disruption of the Dictyostelium myosin heavy chain gene by homologous recombination. Science 236: 1086–1091.

    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 

  • Eng K, Naqvi NI, Wong KC and Balasubramanian MK (1998) Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body. Curr Biol 8: 611–621.

    Google Scholar 

  • Epp JA and Chant J (1997) An IQGAP-related protein controls actinring formation and cytokinesis in yeast. Curr Biol 7: 921–929.

    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, Steinmetz M, Boves H, Kammerer RA, Lottspeich F, Mintert U, Murphy J, Stock A, Aebi U and Gerisch G (1996) Cortexillins, major determinants of cell shape and size, are actin-bundling proteins with a parallel coiled-coil tail. Cell 86: 631–642.

    Google Scholar 

  • Faix J, Clougherty C, Konzok A, Mintert U, Murphy J, Albrecht R, Mühlbauer B and Kuhlmann 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 

  • Field C, Li R and Oegema K (1999) Cytokinesis in eukaryotes: a mechanistic comparison. Curr Opin Cell Biol 11: 68–80.

    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 

  • Gerisch G and Weber I (2000) Cytokinesis without myosin II. Curr Opin Cell Biol 12: 126–132.

    Google Scholar 

  • Glotzer M (1997) The mechanism and control of cytokinesis. Curr Opin Cell Biol 9: 815–823.

    Google Scholar 

  • Hart MJ, Callow MG, Souza B and Polakis P (1996) IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for Cdc42Hs. EMBO J 15: 2997–3005.

    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 of Dictyostelium. Biochem Biophys Res Commun 296: 305–312.

    Google Scholar 

  • Kimura K, Tsuji T, Takada Y, Miki T and Narumiya S (2000) Accumulation of GTP-bound RhoA during cytokinesis and a critical role of ECT2 in this accumulation. J Biol Chem 275: 17,233–17,236.

    Google Scholar 

  • Knecht DA and Loomis WF (1987) Antisense RNA inactivation of myosin heavy chain gene expression in Dictyostelium discoideum. Science 236: 1081–1086.

    Google Scholar 

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

    Google Scholar 

  • Kuroda S, Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A and Kaibuchi K (1996) Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1. J Biol Chem 271: 23,363–23,367.

    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. J Cell Biol 133: 1321–1329.

    Google Scholar 

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

    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 

  • Neujahr R, Albrecht R, Köhler J, Matzner M, Schwartz JM, Westphal M and Gerisch G (1998) Microtubule-mediated centrosome motility and the positioning of cleavage furrows in multinucleate myosin II-null cells. J Cell Sci 111: 1227–1240.

    Google Scholar 

  • Neujahr R, Heizer C and Gerisch G (1997) Myosin II-independent processes in mitotic cells of Dictyostelium discoideum: redistribution of the nuclei, re-arrangement of the actin system and formation of the cleavage furrow. J Cell Sci 110: 123–137.

    Google Scholar 

  • O'Connell CB, Wheatley SP, Ahmed S and Wang YL (1999) The small GTP-binding protein rho regulates cortical activities in cultured cells during division. J Cell Biol 144: 305–313.

    Google Scholar 

  • Palmieri SJ, Nebl T, Pope RK, Seastone DJ, Lee E, Hinchcliffe EH, Sluder 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 Mot Cytoskel 46: 285–304.

    Google Scholar 

  • Prokopenko SN, Brumby A, O'Keefe L, Prior L, He Y, Saint R and Bellen HJ (1999) A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila. Genes Dev 13: 2301–2314.

    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 

  • Rivero F, Albrecht R, Dislich H, Bracco E, Graciotti L, Bozzaro S and Noegel AA (1999) 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, Illenberger D, Somesh BP, Dislich H, Adam N and Meyer A-K (2002) Defects in cytokinesis, actin reorganization and the contractile vacuole in cells deficient in RhoGDI. EMBO J 21: 4539–4549.

    Google Scholar 

  • Robinson DN and Spudich JA (2000) Towards a molecular understanding of cytokinesis. Trends Cell Biol 10: 228–237.

    Google Scholar 

  • Satterwhite LL and Pollard TD (1992) Cytokinesis. Curr Opin Cell Biol 4: 43–52.

    Google Scholar 

  • Simson R, Wallra. E, Faix J, Niewöhner J, Gerisch G and Sackmann E (1998) Membrane bending modulus and adhesion energy of wild-type and mutant cells of Dictyostelium lacking talin or cortexillins. Biophys J 74: 514–522.

    Google Scholar 

  • Steinmetz MO, Stock A, Schulthess T, Landwehr R, Lustig A, Faix J, Gerisch G, Aebi U and Kammerer RA (1998) A distinct 14-residue site triggers coiled-coil formation in cortexillin I. EMBO J 17: 1883–1891.

    Google Scholar 

  • Stock A, Steinmetz MO, Janmey P, Aebi U, Gerisch G, Kammerer RA, Weber I and Faix J (1999) Domain analysis of cortexillin I: actin-bundling, PIP2-binding and the rescue of cytokinesis. EMBO J 18: 5274–5284.

    Google Scholar 

  • Tatsumoto T, Xie X, Blumenthal R, Okamoto I and Miki T (1999) Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis. J Cell Biol 147: 921–928.

    Google Scholar 

  • Tuxworth RI, Cheetham JL, Machesky LM, Spiegelmann GB, Weeks G and Insall RH (1997) Dictyostelium RasG is required for normal motility and cytokinesis, but not growth. J Cell Biol 138: 605–614.

    Google Scholar 

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

    Google Scholar 

  • Weber I, Gerisch G, Heizer C, Murphy J, Badelt K, Stock A, Schwartz JM and Faix J (1999) Cytokinesis mediated through the recruitment of cortexillins into the cleavage furrow. EMBO J 18: 586–594.

    Google Scholar 

  • Weber I, Neujahr R, Du A, Köhler J, Faix J and Gerisch G (2000) Two-step positioning of a cleavage furrow by cortexillin and myosin II. Cur Biol 10: 501–506.

    Google Scholar 

  • Weissbach L, Settleman J, Kalady MF, Snijders AJ, Murthy AE, Yan Y-X and Bernards A (1994) Identification of a human rasGAPrelated protein containing calmodulin-binding motifs. J Biol Chem 269: 20,517–20,521.

    Google Scholar 

  • Zang JH, Cavet G, Sabry JH, Wagner P, Moores SL and Spudich JA (1997) On the role of myosin-II in cytokinesis: division of Dictyostelium cells under adhesive and nonadhesive conditions. Mol Biol Cell 8: 2617–2629.

    Google Scholar 

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  1. A. Butenandt-Institut für Zellbiologie, Ludwig-Maximilians-Universität München, Schillerstrasse 42, 80336, München, Germany

    J. Faix

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Faix, J. The actin-bundling protein cortexillin is the downstream target of a Rac1-signaling pathway required for cytokinesis. J Muscle Res Cell Motil 23, 765–772 (2002). https://doi.org/10.1023/A:1024427712131

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