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 Dictyostelium development are regulated by cAMP, which functions both as an extracellular hormone-like signal and an intracellular second messenger. Previous data indicated that aca- mutants, which lack adenylyl cyclase activity, fail to aggregate and do not express cell-type-specific genes. We show here that overexpression of ACG, a constitutively active adenylyl cyclase, which in wild-type cells is only expressed during spore germination, partially restores the coordination of cell movement and completely restores developmental gene expression. The aca- cells can also be induced to develop into viable spores by synergy with wild-type cells and, furthermore, form small but normal fruiting bodies, after a developmentally relevant regimen of stimulation with nanomolar cAMP pulses followed by micromolar cAMP concentrations. 2'-Deoxy cAMP, a cAMP analog that activates the cell-surface cAMP receptors but not cAMP-dependent protein kinase (PKA), also induces fruiting body formation as well as expression of prespore-specific and prestalk-enriched genes in aca- cells. Intracellular cAMP levels were not altered in aca- cells after stimulation with 2'-deoxy cAMP. Our data indicate that ACA is not required to provide intracellular cAMP for PKA activation but is essential to produce extracellular cAMP for coordination of cell movement during all stages of development and for induction of developmental gene expression.