Effects of cyclic AMP pulses on adenylate cyclase and the phosphodiesterase inhibitor of D. discoideum

Abstract

STARVATION triggers the differentiation of Dictyostelium discoideum amoebae to aggregation competence. The differentiated cells orientate and migrate towards attracting centres, presumably consisting of amoebae which autonomously and rhythmically emit cyclic AMP as a chemotactic signal. Signals, emitted with a periodicity of 5–8 min (refs 1–3, 5), are presumably generated by rhythmic changes in adenylate cyclase activity⁶, levels of which dramatically increase during the first few hours before the expression of aggregation competence^7,8. Cellular responses to external cyclic AMP are probably mediated by plasma membrane receptors⁹. When stimulated by a pulse of cyclic AMP, amoebae amplify¹⁰ and relay^1,5,10,11 the chemotactic signal, which results in a coordinated aggregation. The decay of the chemotactic signal is determined by the activity of the extracellular cyclic AMP phosphodiesterase^12,13 whose activity is modulated by an inhibitor excreted by cells during the early hours of starvation¹⁴. Cyclic AMP pulses have recently also been shown to regulate the differentiation of cells to aggregation competence¹⁵. To determine their mechanism of action, we examined the influence of applied cyclic AMP pulses on the two earliest biochemical events implicated in the control of cyclic AMP levels, the rise in adenylate cyclase activity and the appearance of the extracellular phosphodiesterase inhibitor. The results show that adenylate cyclase may exist in active or inactive forms. Applied cyclic AMP pulses seem to induce cell differentiation by activating the enzyme. They also are shown to repress the production of the phosphodiesterase inhibitor.