title: Genetic and physiologic modulation of the prestarvation response in Dictyostelium discoideum.
abstract: Throughout vegetative growth, Dictyostelium amoebae secrete an autocrine factor, prestarvation factor, PSF, which accumulates in proportion to cell density. During late exponential growth, PSF induces the expression of several genes whose products are needed for cAMP signaling and cell aggregation. Among these genes are discoidin-I and the 2.4-kb transcript of cyclic nucleotide phosphodiesterase (PDE). We have identified several parameters that modulate expression of one or both of these prestarvation response genes; all effects were monitored in cells growing exponentially on bacteria. Under these conditions, axenic mutants produce higher levels of PSF activity than wild-type cells. Consistent with the high PSF levels, the 2.4-kb PDE transcript is more abundant in axenic strains than wild-type cells at the same cell density. In contrast, the density-dependent induction of discoidin-I is greatly delayed in axenic strains, occurring only at the very end of exponential growth. Analysis of axenic strains of independent origin suggested that this negative effect on discoidin-I expression is attributable to the axenic mutations themselves. The effects of two environmental factors that inhibit the prestarvation response (the bacteria upon which the cells feed and a bacterial product, folic acid) were also analyzed. We found that folate does not account for the inhibitory effect of bacteria. Cells deficient in the G-protein beta subunit, which is thought to be common to all heterotrimeric G-proteins in Dictyostelium, respond to PSF in the same manner as G beta+ cells, and this response is inhibited by bacteria. However, folate has no inhibitory effect on g beta- cells, indicating that folate inhibition is mediated by a heterotrimeric G-protein. In cells lacking the catalytic subunit of protein kinase A, the prestarvation response is severely impaired, but about 3% of the pka- cells manifest an apparently normal density-dependent induction of discoidin-I. This behavior and the heterogeneity of the prestarvation response in wild-type cells lead us to speculate that protein kinase A may not be required for PSF signal transduction per se, but rather may render the cells responsive to PSF. Based on analysis of adenylyl cyclase mutants (aca-), the effect of protein kinase A is not cAMP-dependent.
authors.affiliation: Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
authors.forename: V
authors.initials: V
authors.lastname: Burdine
authors.forename: M
authors.initials: M
authors.lastname: Clarke
mesh_terms: D000630:Aminopterin / Q000494:pharmacology; D000818:Animals; D001375:Azaguanine / Q000494:pharmacology; D001685:Biological Factors / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002452:Cell Count; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000502:physiology*; D000070821:Discoidins; D005492:Folic Acid / Q000494:pharmacology; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D007711:Klebsiella pneumoniae; D037102:Lectins; D008727:Methotrexate / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: D001685:Biological Factors; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D000070821:Discoidins; D005656:Fungal Proteins; D037102:Lectins; D015800:Protozoan Proteins; C052291:cell cohesion molecule, Dictyostelium; D005492:Folic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D000630:Aminopterin; D001375:Azaguanine; D008727:Methotrexate