title: Glycogen synthase kinase-3 (GSK-3) is regulated during Dictyostelium development via the serpentine receptor cAR3.
abstract: Glycogen synthase kinase-3 (GSK-3) is required during metazoan development to mediate the effects of the extracellular signal wingless/Wnt-1 and hence is necessary for correct cell type specification. GSK-3 also regulates cell fate during Dictyostelium development, but in this case it appears to mediate the effects of extracellular cAMP. By direct measurement of GSK-3 kinase activity during Dictyostelium development, we find that there is a rise in activity at the initiation of multicellular development which can be induced by cAMP. The timing of the rise correlates with the requirement for the Dictyostelium homologue of GSK-3, GSKA, to specify cell fate. We show that loss of the cAMP receptor cAR3 almost completely abolishes the rise in kinase activity and causes a mis-specification of cell fate that is equivalent to that seen in a gskA- mutant. The phenotype of a cAR3(-) mutant however is less severe than loss of gskA and ultimately gives rise to an apparently wild-type fruiting body. These results indicate that in Dictyostelium extracellular cAMP acts via cAR3 to cause a rise in GSKA kinase activity which regulates cell type patterning during the initial stages of multicellularity.
authors.affiliation: Dipartemento di Biologia Evolutiva, University di Siena, Siena, Italia.
authors.forename: S E
authors.initials: SE
authors.lastname: Plyte
authors.forename: E
authors.initials: E
authors.lastname: O'Donovan
authors.forename: J R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: A J
authors.initials: AJ
authors.lastname: Harwood
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007763:Lac Operon / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011953:Receptors, Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014170:Transformation, Genetic
chemical_list: C079747:CAR3 protein, Dictyostelium discoideum; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3