Antagonistic effects of signal transduction by intracellular and extracellular cAMP on gene regulation in Dictyostelium.

In Dictyostelium, cAMP plays a role as an intracellular second messenger and in addition, as an extracellular first messenger. Both functions are thought to be tightly linked because adenylyl cyclase is coupled via G-proteins to the cell surface cAMP receptor cAR 1. Using the discoidin I gene family as a molecular marker for the first stages of development, we show here that induction of transcription requires the G-protein subunit alpha 2 and thus an as yet unidentified surface receptor, CRAC (cytosolic regulator of adenylyl cyclase), and PKA. Induction can be conferred by an increase in intracellular cAMP. In contrast, transcriptional down-regulation occurs by stimulation of cAR 1 with extracellular cAMP and a subsequent, G-protein-independent Ca2+ influx. In a G alpha 2 gene disruption mutant, discoidin I expression can be efficiently modulated by analogues simulating intracellular cAMP (discoidin induction) and extracellular cAMP (discoidin down-regulation). We thus demonstrate possible antagonistic functions of intra- and extracellular cAMP.