EXTRACELLULAR CAMP CAN RESTORE DEVELOPMENT IN DICTYOSTELIUM CELLS LACKING ONE, BUT NOT 2 SUBTYPES OF EARLY CAMP RECEPTORS (CARS) - EVIDENCEFOR INVOLVEMENT OF CAR1 IN AGGREGATIVE GENE-EXPRESSION

Extracellular cAMP induces expression of several classes of developmen tally regulated genes in Dictyostelium. Four highly homologous surface cAMP receptors (cARs) were identified earlier, but involvement of spe cific cARs in gene regulation has not been clarified. Cells lacking th e chemotactic receptor, cAR1, neither aggregate nor express developmen tally regulated genes. Expression of aggregative genes is in wild-type cells induced by nanomolar cAMP pulses and repressed by persistent mi cromolar cAMP stimuli, which induce expression of prespore and prestal k-enriched genes during the postaggregative stages of development. We show here that in cell lines carrying a cAR1 gene disruption, nanomola r pulses cannot induce aggregative gene expression. Remarkably, microm olar cAMP can induce expression of aggregative genes in car1(-) cells as well as expression of prespore and prestalk-enriched genes, and fur thermore restores their ability to form normal slugs and fruiting bodi es. These data indicate that cAR1 mediates aggregative but not postagg regative gene expression and morphogenesis, and suggest that after gen e disruption, its function is partially taken over by a lower affinity receptor that is not subjected to desensitization. The absence of ano ther early cAMP receptor, cAR3, does not affect development. However, in a car1(-)/car3(-) double mutant, cAMP stimulation cannot restore an y developmental gene expression, indicating that cAR3 may have substit uted for cAR1 in car1(-) cell lines.