Skip to main content
Log in

Signal transduction and motility ofDictyostelium

  • Intracellular Traffic
  • Published:
Bioscience Reports

Abstract

This review is concerned with the roles of cyclic GMP and Ca2+ ions in signal transduction for chemotaxis ofDictyostelium. These molecules are involved in signalling between the cell surface cyclic AMP receptors and cytoskeletal myosin II involved in chemotactic cell movement. Evidence is presented for uptake and/or eflux of Ca2+ being regulated by cyclic GMP. The link between Ca2+, cyclic GMP and chemotactic cell movement has been explored using “streamer F” mutants whose primary defect is in the structural gene for the cyclic GMP-specific phosphodiesterase. This mutation causes the mutants to produce an abnormally prolonged peak of cyclic GMP accumulation in response to stimulation with the chemoattractant cyclic AMP. The production and relay of cyclic AMP signals is normal in these mutants, but certain events associated with movement are (like the cyclic GMP response) abnormally prolonged in the mutants. These events include Ca2+ uptake, myosin II association with the cytoskeleton and regulation of both myosin heavy and light chain phosphorylation. These changes can be correlated with changes in the shape of the amoebae after chemotactic stimulation. Other mutants in which the accumulation of cyclic GMP in response to cyclic AMP stimulation was absent produced no myosin II responses.

A model is described in which cyclic GMP (directly or indirectly via Ca2+) regulates accumulation of myosin II on the cytoskeleton by regulating phosphorylation of the myosin heavy and light chain kinases.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Berlot, C. H., Spudich, J. A. and Devreotes, P. N. (1985) Chemoattractant-elicited increases in myosin phosphorylation inDictyostelium.Cell 43:307–314.

    Google Scholar 

  • Berlot, C. H., Devreotes, P. N. and Spudich, J. A. (1987) Chemoattractant elicited increases inDictyostelium myosin phosphorylation are due to changes in myosin localization and increases in kinase activity.J. Biol. Chem. 262:3918–3926.

    Google Scholar 

  • Bominaar, A. A., Kesbeke, F., Snaarjagalska, B. E., Peters, D. J. M., Schaap, P. and Vanhaastert, P. J. M. (1991) Aberrant chemotaxis and differentiation inDictyostelium: MutantfgdC with a defective regulation of receptor-stimulated phosphoinositidase-C.J. Cell Sci. 100:825–831.

    Google Scholar 

  • Chia, C., Shariff, A., Savage, S. and Luna, E. (1993) The integral membrane protein, ponticulin, acts as a monomer in nucleating actin assembly.J. Cell Biol. 120:909–922.

    Google Scholar 

  • Condeelis, J., Hall, A., Bresnick, A., Warren, V., Hock, R., Bennet, H. and Ogihara, S. (1988) Actin polymerization and pseudopod extension during amoeboid chemotaxis.Cell Motility and Cytoskeleton 10:77–90.

    Google Scholar 

  • Côté, G. P. and McCrea, S. M. (1987) Selective removal of the carboxyl-terminal tail end of theDictyostelium myosin II heavy chain by chymotrypsin.J. Biol. Chem. 262:13,033–13,038.

    Google Scholar 

  • Coukell, M. B. and Cameron, A. M. (1986) Characterization of revertants of stmF mutants ofDictyostelium discoideum: evidence that stmF is the structural gene of the cGMP-specific phosphodieasterase.Devel. Genet. 6:163–177.

    Google Scholar 

  • De Lozanne, A. and Spudich, J. A. (1987) Disruption of theDictyostelium myosin heavy chain gene by homologous recombination.Science 236:1086–1091.

    Google Scholar 

  • Devreotes, P. N. (1983) Cyclic nucleotides and cell-cell communication inDictyostelium discoideum. In:Advances in Cyclic Nucleotide Research Vol. 15 (eds) P. Greengard and G. A. Robison New York: Raven Press pp. 55–96.

    Google Scholar 

  • Egelhoff, T. T., Lee, R. J. and Spudich, J. A. (1993)Dictyostelium myosin heavy chain phosphorylation sites regulate myosin filament assembly and localizationin vivo.Cell 75:363–371.

    Google Scholar 

  • Europe-Finner, G. N. and Newell, P. C. (1984) Inhibition of aggregation inDictyostelium by EGTA-induced depletion of calcium.FEMS Microbiol. Letts. 21:21–25.

    Google Scholar 

  • Europe-Finner, G. N. and Newell, P. C. (1985) Inositol (1,4,5)trisphosphate induces cyclic GMP formation inDictyostelium discoideum.Biochem. Biophys. Res. Commun. 130:1115–1122.

    Google Scholar 

  • Europe-Finner, G. N. and Newell, P. C. (1986) Inositol (1,4,5)-trisphosphate induces calcium release from a non-mitochondrial pool in amoebae ofDictyostelium.Biochim. et Biophys. Acta 887:335–340.

    Google Scholar 

  • Flaadt, H., Jaworski, E., Schlatterer, C. and Malchow, D. (1993) Cyclic AMP- and Ins 145 P3-induced Ca2+ fluxes in permeabilised cells ofDictyostelium discoideum. cGMP regulates Ca2+ entry across the plasma membrane.J. Cell Sci. 105:255–261.

    Google Scholar 

  • Franke, J. and Kessin, R. H. (1992) The cyclic nucleotide phosphodieasterase ofDictyostelium discoideum: molecular genetics and biochemistry.Cellular Signalling 4:471–478.

    Google Scholar 

  • Gerisch, G., Malchow, D., Huesgen, A., Nanjundiah, V., Roos, W. and Wick, U. (1975) Cyclic AMP reception and cell recognition inDictyostelium discoideum. In:Developmental Biology ICN-UCLA Symposia on Molecular and Cellular Biology Vol. 2 (eds) D. McMahon and C. F. Fox New York: W. A. Benjamin Inc. pp. 76–88.

    Google Scholar 

  • Gerisch, G., Albrecht, R., De Hostos, E., Wallraff, E., Heizer, C., Kreitmeier, M. And Müller-Taubenberger, A. (1993) Actin-associated proteins in motility and chemotaxis ofDictyostelium cells inCell Behaviour: Adhesion and Motility (eds) G Jones, C. Wigley and R. Warn,SEB Symposium 47:297–315.

    Google Scholar 

  • Griffith, L. M., Downs, S. M. and Spudich, J. A. (1987) Myoslin light chain kinase and myosin light chain phosphatase fromDictyostelium: Effects of reversible phosphorylation on myosin structure and function.J. Cell Biol. 104:1309–1323.

    Google Scholar 

  • Hall, A. L., Schlein, A. and Condeelis, J. (1988) Relationship of pseudopod extension to chemotactic hormone-induced actin polymerization in amoeboid cells.Journal of Cellular Biochemistry,37:285–299.

    Google Scholar 

  • Hall, A. L., Warren, V., Dharmawardhane, S. and Condeelis, J. (1989) Identification of actin nucleation activity and polymerization inhibitor in ameboid cells: their regulation by chemotactic stimulation.J. Cell Biol. 109:2207–2214.

    Google Scholar 

  • Haugwitz, M., Noegel, A. A., Rieger, D., Lottspeich, F. and Schleicher, M. (1991)Dictyostelium discoideum contains two profilin isoforms that differ in structure and function.J. Cell Sci. 100:481–48.

    Google Scholar 

  • Janssens, P. M. W. and Van Haastert, P. J. M. (1987) Molecular basis of transmembrane signal transduction inDictyostelium discoideum.Microbiol. Rev. 51:396–418.

    Google Scholar 

  • Janssens, P. M. W. and De Jong, C. C. C. (1988) A magnesium-dependent guanylate cyclase in cell free preparations ofDictyostelium discoideum.Biochem. Biophys. Res. Commun. 150:405–411.

    Google Scholar 

  • Jay, P. Y., Pham, P. A., Wong, S. C. and Elson, E. L. (1995) A mechanical function of myosin II in cell motility.J. Cell Sci. 108:387–393.

    Google Scholar 

  • Kessin, R. H. (1988) Genetics of earlyDictyostelium discoideum development.Microbiol. Rev. 52:29–49.

    Google Scholar 

  • Knecht, D. A. and Loomis, W. F. (1987) Antisense RNA inactivation of myosin heavy chain gene expression inDictyostelium discoideum.Science 236:1081–1085.

    Google Scholar 

  • Knecht, D. A. and Loomis, W. F. (1988) Developmental consequences of the lack of myosin heavy chain inDictyostelium discoideum.Dev. Biol. 128:178–184.

    Google Scholar 

  • Kuczmarski, E. R., Tafuri, S. R. and Parysek, L. M. (1987) Effect of heavy chain phosphorylation on the polymerization and structure ofDictyostelium myosin filaments.J. Cell Biol. 105:2989–2997.

    Google Scholar 

  • Kuczmarski, E. R. and Spudich, J. A. (1980) Regulation of myosin self-assembly: Phosphorylation ofDictyostelium heavy chain inhibits formation of thick filaments.Proc. Natl. Acad. Sci. USA 77:7292–7296.

    Google Scholar 

  • Kumagai, A., Pupillo, M., Gunderson, R., Miake-Lye, R., Devreotes, P. N. and Firtel, R. A. (1989) Regulation and function of Gα protein subunits inDictyostelium.Cell 57:265–275.

    Google Scholar 

  • Liu, G., Kuwayama, H., Ishida, S. and Newell, P. C. (1993) The role of cyclic GMP in regulating myosin during chemotaxis ofDictyostelium: Evidence from a mutant lacking the normal cyclic GMP response to cyclic AMP.J. Cell Sci. 106:591–596.

    Google Scholar 

  • Liu, G. and Newell, P. C. (1988) Evidence that cyclic GMP regulates myosin interaction with the cytoskeleton during chemotaxis ofDictyostelium.J. Cell Sci. 90:123–129.

    Google Scholar 

  • Liu, G. and Newell, P. C. (1991) Evidence that cyclic GMP may regulate the association of Myosin-II heavy chain with the cytoskeleton by inhibiting its phosphorylation.J. Cell Sci. 98:483–490.

    Google Scholar 

  • Liu, G. and Newell, P. C. (1993) Role of cyclic GMP in signal transduction to cytoskeletal myosin inCell Behaviour: Adhesion and Motility (eds) G. Jones, C. Wigley, and R. Warn, SEB Symposium47:283–295.

  • Liu, G. and Newell, P. C. (1994) Regulation of myosin regulatory light chain phosphorylation via cyclic GMP during chemotaxis ofDictyostelium.J. Cell Sci. 107:1737–1743.

    Google Scholar 

  • Lück-Vielmetter, D., Schleicher, M., Grabatin, B., Wippler, J. and Gerisch, G. (1990) Replacement of threonines residues by serine and alanine in a phosphorylatable heavy chain fragment ofDictyostelium myosin II,FEBS Lett. 269:239–243.

    Google Scholar 

  • Malchow, D., Bohme, R. and Rahmsdorf, H. J. (1981) Regulation of phosphorylation of myosin heavy chair during the chemotactic response ofDictyostelium cells.Eur. J. Biochem. 117:213–218.

    Google Scholar 

  • Malchow, D., Bohme, R. and Gras, U. (1982) On the role of calcium in chemotaxis and oscillations ofDictyostelium cells.Biophys. Struct. Mech. 9:131–136.

    Google Scholar 

  • Manstein, D. J., Titus, M. A., De Lozanne, A. and Spudich, J. A. (1989) Gene replacement inDictyostelium: generation of myosin null mutants.EMBO J. 8:923–932.

    Google Scholar 

  • Maruta, H., Baltes, W., Dieter, P., Marme, D. and Gerisch, G. (1983) Myosin heavy chain kinase inactivated by Ca2+ calmodulin from aggregating cells ofDictyostelium discoideum.EMBO J. 2:535–542.

    Google Scholar 

  • Mason, J., Rasmussen, W. H. and Dibella, F. (1971) 3′∶5′AMP and Ca2+ in slime mold aggregation.Exp. Cell Res. 67:156–160.

    Google Scholar 

  • Mato, J. M., Krens, F. A., Van Haastert, P. J. M. and Konijn, T. M. (1977) 3′∶5′-Cyclic AMP-dependent 3′∶5′-cyclic GMP accumulation inDictyostelium discoideum.Proc. Natl. Acad. Sci. USA 74:2348–2351.

    Google Scholar 

  • McRobbie, S. J. and Newell, P. C. (1983) Changes in actin associated with cytoskeleton following chemotactic stimulation ofDictyostelium discoideum.Biochem. Biophys. Res. Commun. 115:351–359.

    Google Scholar 

  • McRobbie, S. J. and Newell, P. C. (1984a) Chemoattractant-mediated changes in cytoskeletal actin of cellular slime moulds.J. Cell Sci. 68:139–151.

    Google Scholar 

  • McRobbie, S. J. and Newell, P. C. (1984b). A new model for chemotactic signal transduction inDictyostelium discoideum.Biochem. Biophys. Res. Commun. 123:1076–1083.

    Google Scholar 

  • McRobbie, S. J. and Newell, P. C. (1985) Effect of cytochalasin B on cell movements and chemoattractant elicited actin changes inDictyostelium.Exp. Cell Res. 160:275–286.

    Google Scholar 

  • Menz, S., Bumann, J., Jaworski, E. and Malchow, D. (1991) Mutant analysis suggests that cyclic GMP mediates the cyclic AMP-induced Ca2+ Uptake inDicyostelium.J. Cell Sci. 99:187–191.

    Google Scholar 

  • Milne, J. L. and Coukell, M. B. (1991) A Ca2+ transport system associated with the plasma membrane ofDictyostelium discoideum is activated by different chemoattractant receptors.J. Cell Biol. 112:103–110.

    Google Scholar 

  • Nanjundiah, V. (1985) The evolution of communication and social behaviour inDictyostelium discoideum.Proc. Indian Acad. Sci. (Anim. Sci.) 94:639–653.

    Google Scholar 

  • Newell, P. C. (1986a) The role of actin polymerization in amoebal chemotaxis.Bioessays 5:208–211.

    Google Scholar 

  • Newell, P. C. (1986b) Receptors for cell communication inDictyostelium; inHormones, receptors and cellular interaction in Plants (eds) C. M. Chadwick and D. R. Garrod (Cambridge Univ. Press) pp. 154–216.

  • Newell, P. C., Europe-Finner, G. N. and Small, N. V. (1987) Signal transduction during amoebal chemotaxis ofDictyostelium discoideum.Microbiological Sci. 4:5–11.

    Google Scholar 

  • Newell, P. C., Europe-Finner, G. N., Small, N. V. and Liu, G. (1988) Inositol phosphates, G-proteins andras genes involved in chemotactic signal transduction ofDictyostelium.J. Cell Sci,89:123–127.

    Google Scholar 

  • Newell, P. C. and Liu, G. (1992) Streamer F mutants and chemotaxis ofDictyostelium.Bioessays 14:473–479.

    Google Scholar 

  • Nishikawa, M., de Lanerolle, P., Lincoln, T. M. and Adelstein, R. S. (1984) Phosphorylation of mammalian myosin light chain kinases by the catalytic subunit of cyclic AMP-dependent protein kinase and by cyclic GMP-dependent protein kinase.J. Biol. Chem. 259:8,429–8,436.

    Google Scholar 

  • Nishikawa, M., Shirakawa, S. and Adelstein, R. S. (1985) Phosphorylation of smooth muscle light chain kinase by protein kinase C.J. Biol. Chem. 260:8,978–8,983.

    Google Scholar 

  • Padh, H. and Brenner, M. (1984) Studies of the guanylate cyclase of the social amoebaDictyostelium discoideum.Arch. Biochem. Biophys. 229:73–80.

    Google Scholar 

  • Pasternak, C., Flicker, P. F., Ravid, S. and Spudich, J. A. (1989) Intermolecular versus intramolecular interactions ofDictyostelium myosin: Possible regulation by heavy chain phosphorylation.J. Cell Biol. 109:203–210.

    Google Scholar 

  • Ravid, S. and Spudich, J. A. (1989) Myosin heavy chain kinase from developedDictyostelium cells. Purification and characterization.J. Biol. Chem. 264:15,144–50.

    Google Scholar 

  • Ravid, S. and Spudich, J. A. (1992) Membrane-boundDictyostelium myosin heavy chain kinase: A developmentally regulated substrate-specific member of the protein kinase C family;Proc. Natl. Acad. Sci. USA. 89:5,877–5,881.

    Google Scholar 

  • Ross, F. M. and Newell, P. C. (1979) Genetics of aggregation pattern mutations in the cellular slime mouldDictyostelium discoideum.J. Gen. Microbiol. 115:289–300.

    Google Scholar 

  • Ross, F. M. and Newell, P. C. (1981) Streamers: Chemotactic mutants ofDictyostelium discoideum with altered cyclic GMP metabolism.J. Gen. Microbiol. 127:339–350.

    Google Scholar 

  • Saito, M. (1979) Effect of extracellular Ca2+ on the morphogenesis ofDictyostelium discoideum;Exp. Cell Res. 123:79–86.

    Google Scholar 

  • Schlatterer, C. and Malchow, D. (1993) Intracellular guanosine-5′-O-3-thiotriphosphate blocks chemotactic motility ofDictyostelium discoideum amobae.Cell Motil. and Cytoskel. 25:298–307.

    Google Scholar 

  • Segall, J. E. (1992) Behavioural responses of streamer F mutants ofDictyostelium discoideum- Effects of cyclic GMP on cell motility.J. Cell Sci. 101:589–597.

    Google Scholar 

  • Shelden, E. and Knecht, D. A. (1995) Mutants lacking myosin II cannot resist forces generated during multicellular morphogenesis.J. Cell Sci. 108:1105–1115.

    Google Scholar 

  • Small, N. V., Europe-Finner, G. N. and Newell, P. C. (1986) Calcium induces cyclic GMP formation inDictyostelium.FEBS Lett. 203:11–14.

    Google Scholar 

  • Tan, J. L. and Spudich, J. A. (1990)Dictyostelium myosin light chain kinase: Purification and characterization.J. Biol. Chem. 265:13,818–13,824.

    Google Scholar 

  • Tan, J. L. and Spudich, J. A. (1991) Characterization and bacterial expression of theDictyostelium myosin light chain kinase cDNA: Identification of an autoinhibitory domain.J. Biol. Chem. 266:16,044–16,049.

    Google Scholar 

  • Unterweger, N. and Schlatterer, C. (1994) Introduction of calcium buffers into the cytosol ofDictyostelium discoideum amoebae alters cell morphology and inhibits chemotaxis.Cell Calcium 17:97–110.

    Google Scholar 

  • Van Duijn, B. and Van Haastert, P. J. M. (1992) Independent control of locomotion and orientation duringDictyostelium discoideum chemotaxis.J. Cell Sci. 102:763–768.

    Google Scholar 

  • Van Haastert, P. J. M. and Konijn, T. M. (1982) Signal transduction in the cellular slime molds.Mol. Cell. Endocrinol. 26:1–17.

    Google Scholar 

  • Van Haastert, P. J. M., Van Lookeren Campagne, M. M. and Kesbeke, F. (1983) Multiple degradation pathways of chemoattractant mediated cyclic GMP accumulation inDictyostelium.Biochim. et Biophys. Acta 756:67–71.

    Google Scholar 

  • Van Haastert, P. J. M., Van Lookeren Campagne, M. M. and Ross, F. M. (1982) Altered cGMP-phosphodiesterase activity in chemotactic mutants ofDictyostelium discoideum.FEBS Letters,147:149–152.

    Google Scholar 

  • Wanner, R. and Wurster, B. (1990) Cyclic GMP-activated protein kinase fromDictyostelium discoideum Biochim. Biophys. Acta 1053:179–184.

    Google Scholar 

  • Wessels, D., Soll, D. R., Knecht, D., Loomis, W. F., De Lozanne, A. and Spudich, J. (1988) Cell motility and chemotaxis inDictyostelium amebae lacking myosin heavy chain;Dev. Biol. 128:164–177.

    Google Scholar 

  • Wurster, B., Schubiger, K., Wick, U. and Gerisch, G. (1977) Cyclic GMP inDictyostelium discoideum. Oscillations and pulses in response to folic acid and cyclic AMP signals.FEBS Lett. 76:141–144.

    Google Scholar 

  • Yumura, S. and Kitanishi-Yumura, T. (1992) Release of myosin from the membrane-cytoskeleton ofDictyostelium discoideum mediated by heavy-chain phosphorylation at foci within the cortical actin network.J. Cell Biol. 117:1231–1239.

    Google Scholar 

  • Yumura, S. and Kitanishi-Yumura, T. (1993) A mechanism for the intracellular localization of myosin II filaments in theDictyostelium amoeba.J. Cell Sci. 105:233–242.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Newell, P.C. Signal transduction and motility ofDictyostelium . Biosci Rep 15, 445–462 (1995). https://doi.org/10.1007/BF01204348

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01204348

Key words

Navigation