A pharmacologically distinct cyclic AMP receptor is responsible for the regulation of gp80 expression in Dictyostelium discoideum.
The EDTA-resistant cell-cell adhesion expressed at the aggregation stage of Dictyostelium discoideum is mediated by a cell surface glycoprotein of Mr 80,000 (gp80). The expression of gp80 is developmentally regulated by cyclic AMP (cAMP). In vitro nuclear run-on experiments show that transcription of the gp80 gene is initiated soon after the onset of development. The basal level of gp80 transcription is significantly augmented by exogenous cAMP pulses. Interestingly, in analog studies, 2'-deoxy-cAMP, 8-bromo-cAMP, and N6-monobutyryl-cAMP are all capable of inducing a rapid accumulation of gp80 mRNA, suggesting the presence of a unique cAMP receptor that responds equally well to these analogs. To determine whether intracellular cAMP plays a role in the regulation of gp80 expression, caffeine was used to block cAMP-induced receptor-mediated adenylate cyclase activation. Expression of gp80 mRNA was blocked in caffeine-treated cells but could be substantially restored by treatment with exogenous cAMP pulses, suggesting that adenylate cyclase activation is not required. gp80 expression was also examined in the signal transduction mutants synag 7 and frigid A. In both mutants, gp80 was expressed at the basal level. Pulses of cAMP as well as 2'-deoxy-cAMP and N6-monobutyryl-cAMP were capable of restoring the normal level of gp80 expression in synag 7 cells. These results, taken together, indicate bimodal regulation of gp80 expression during development and the involvement of a novel cAMP receptor in the transmembrane signalling pathway that regulates gp80 gene expression.
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Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
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D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D007700:Kinetics; D015800:Protozoan Proteins; D012333:RNA, Messenger / Q000235:genetics; D011953:Receptors, Cyclic AMP / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D015815:Cell Adhesion Molecules; D015800:Protozoan Proteins; D012333:RNA, Messenger; D011953:Receptors, Cyclic AMP; C052291:cell cohesion molecule, Dictyostelium; D000242:Cyclic AMP