Unified mechanism for relay and oscillation of cyclic AMP in Dictyostelium discoideum

Abstract

A modified version of an allosteric model for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] previously analyzed for sustained oscillations of adenosine 3':5'-cyclic monophosphate (cAMP) in Dictyostelium discoideum [Goldbeter, A. (1975) Nature 253, 540-542] is examined to see whether it can account for the relay of cAMP pulses. Oscillations occur around a nonequilibrium, unstable stationary state when system parameters are in a certain domain. It is found that relay can occur outside this domain, in a restricted set of parameter values for which the solution ultimately tends to a stable steady state. A suprathreshold level of extracellular cAMP is needed to elicit relay which consists in a pulsatory synthesis of intracellular cAMP. Theoretical predictions are compared with the results of experiments on cAMP relay and oscillation in aggregation-competent cells of D. discoideum. The model suggests an explanation for the emergence of aggregation centers and for a sequence of developmental events observed in interphase amoebae.