A cell number-counting factor regulates group size in Dictyostelium by differentially modulating cAMP-induced cAMP and cGMP pulse sizes

A secreted counting factor (CF), regulates the size of Dictyostelium discoi deum fruiting bodies in part by regulating cell-cell adhesion. Aggregation and the expression of adhesion molecules are mediated by relayed pulses of cAMP. Cells also respond to cAMP with a short cGMP pulse. We find that CF s lowly down-regulates the cAMP-induced cGMP pulse by inhibiting guanylyl cyc lase activity. A 1-min exposure of cells to purified CF increases the cAMP- induced cAMP pulse. CF does not affect the cAMP receptor or its interaction with its associated G proteins or the translocation of the cytosolic regul ator of adenylyl cyclase to the membrane in response to cAMP. Pulsing strea ming wild-type cells with a high concentration of cAMP results in the forma tion of small groups, whereas reducing cAMP pulse size with exogenous cAMP phosphodiesterase during stream formation causes cells to form large groups . Altering the extracellular cAMP pulse size does not phenocopy the effects of CF on the cAMP-induced cGMP pulse size or cell-cell adhesion, indicatin g that CF does not regulate cGMP pulses and adhesion via CF's effects on cA MP pulses. The results suggest that regulating cell-cell adhesion, the cGMP pulse size, or the cAMP pulse size can control group size and that CF regu lates all three of these independently.