Figure 13

Hypothetical scheme for Ca²⁺-oscillations in Dictyostelium and a link to adenylylcyclase. Adenylylcyclase was shown to be activated by G_βγ, rasC, and CRAC. PI₃K activity provides for PIP₃ allowing cytosolic CRAC to bind to the plasma membrane. Aimless and RipA are thought to act in concert with rasC. The direct target of pianissimo is not yet known nor the detailed sequence of events leading to cAMP synthesis. ERK2 stimulation by cAR1 is independent of rasC [8]. ERK2 inhibits RegA, a cytosolic phosphodiesterase. cAR1 also activates phospholipase A₂ that liberates fatty acids (FA) and elicits Ca²⁺-influx [17, 26]. Ca²⁺ released by fatty acids from the acidic store activates a positive feedback loop via PLC activity. IP₃ stimulates Ca²⁺-release from the ER, thereby raising cytosolic Ca²⁺ and enhancing PLC activity. Ca²⁺ sinks are provided by Ca²⁺-uptake into the ER and the acidic Ca²⁺-store. Inhibition of either pump, the Ca²⁺-pump by XeC or the H⁺-pump by CMA leads to an increase of [Ca²⁺]_i and to a blockade of Ca²⁺-oscillation as well as cAMP relay [48]. ACA is suggested to be activated by a CalDAG stimulated exchange factor acting on RasC. cAMP released to the outside of the cell elicits feed back stimulation during oscillation in cell suspension. Extracellular phosphodiesterase (PdsA) provides for a low extracellular cAMP level allowing sensitive detection of the next wave.