EXTRACELLULAR CAMP IS SUFFICIENT TO RESTORE DEVELOPMENTAL GENE-EXPRESSION AND MORPHOGENESIS IN DICTYOSTELIUM CELLS LACKING THE AGGREGATION ADENYLYL-CYCLASE (ACA)

Cell movement and cell-type-specific gene expression during Dictyostel ium development are regulated by cAMP, which functions both as an extr acellular hormone-like signal and an intracellular second messenger. P revious data indicated that aca- mutants, which lack adenylyl cyclase activity, fail to aggregate and do not express cell-type-specific gene s. We show here that overexpression of ACG, a constitutively active ad enylyl cyclase, which in wild-type cells is only expressed during spor e germination, partially restores the coordination of cell movement an d completely restores developmental gene expression. The aca- cells ca n also be induced to develop into viable spores by synergy with wild-t ype cells and, furthermore, form small but normal fruiting bodies, aft er a developmentally relevant regimen of stimulation with nanomolar cA MP pulses followed by micromolar cAMP concentrations. 2'-Deoxy cAMP, a cAMP analog that activates the cell-surface cAMP receptors but not cA MP-dependent protein kinase (PKA), also induces fruiting body formatio n as well as expression of prespore-specific and prestalk-enriched gen es in aca- cells. Intracellular cAMP levels were not altered in aca- c ells after stimulation with 2'-deoxy cAMP. Our data indicate that ACA is not required to provide intracellular cAMP for PKA activation but i s essential to produce extracellular cAMP for coordination of cell mov ement during all stages of development and for induction of developmen tal gene expression.