An adenylyl cyclase that functions during late development of Dictyostelium

A variety of extracellular signals lead to the accumulation of cAMP which c an act as a second message within cells by activating protein kinase A (PKA ), Expression of many of the essential developmental genes in Dictyostelium discoideum are known to depend on PK4 activity. Cells in which the recepto r-coupled adenyl;yl cyclase gene, acaA, is genetically inactivated grow wel l but are unable to develop, Surprisingly, acaA(-) mutant cells can be resc ued by developing them in mixtures with wild-type cells, suggesting that an other adenylyl cyclase is present in developing cells that can provide the internal cAMP necessary to activate PE;A, However, the only other known ade nylyl cyclase gene in Dictyostelium, acgA, is only expressed during germina tion of spores and plays no role in the formation of fruiting bodies. By sc reening morphological mutants generated by Restriction Enzyme Mediated Inte gration (REMI) me discovered a novel adenylyl cyclase gene, acrA, that is e xpressed at low levels in growing cells and at more than 25-fold higher lev els during development. Growth and development up to the slug stage are una ffected in acrA(-) mutant strains but the cells make almost no viable spore s and produce unnaturally long stalks. Adenylyl cyclase activity increases during aggregation, plateaus during the slug stage and then increases consi derably during terminal differentiation. The increase in activity following aggregation fails to occur in acrA(-) cells. As long as ACA is fully activ e, ACR is not required until culmination but then plays a critical role in sporulation and construction of the stalk.