ROLE OF PKA IN THE TIMING OF DEVELOPMENTAL EVENTS IN DICTYOSTELIUM CELLS

The cyclic AMP (cAMP)-dependent protein kinase, PKA, is dispensable fo r growth of Dictyostelium cells but plays a variety of crucial roles i n development. The catalytic subunit of PKA is inhibited when associat ed with its regulatory subunit brit is activated when cAMP binds to th e regulatory subunit. Deletion of pkaR or overexpression of the gene e ncoding the catalytic subunit, pkaC, results in constitutive activity. Development is independent of cAMP in strains carrying these genetic alterations and proceeds rapidly to the formation of both spores and s talk cells. However, morphogenesis is aberrant in these mutants. In th e wild type, PKA activity functions in a circuit that can spontaneousl y generate pulses of cAMP necessary for long-range aggregation. It is also essential for transcriptional activation of both prespore and pre stalk genes during the slug stage. During culmination, PKA functions i n both prespore and prestalk cells to regulate the relative timing of terminal differentiation. A positive feedback loop results in the rapi d release of a signal peptide, SDF-2 when prestalk cells are exposed t o low levels of SDF-2. The signal transduction pathway that mediates t he response to SDF-2 in both prestalk and prespore cells involves the two-component system of DhkA and RegA. When the cAMP phosphodiesterase RegA is inhibited, cAMP accumulates and activates PKA, leading to vac uolation of stalk cells and encapsulation of spores. These studies ind icate that multiple inputs regulate PKA activity to control the relati ve timing of differentiations in Dictyostelium.