Modeling oscillations and waves of cAMP in Dictyostelium discoideum cells

Abstract

We examine the theoretical aspects of temporal and spatiotemporal organization in the cAMP signaling system of Dictyostelium discoideum amoebae which aggregate in a wavelike manner after starvation, in response to pulses of cAMP emitted with a periodicity of several minutes by cells behaving as aggregation centers. We first extend the model based on receptor desensitization, previously proposed by Martiel and Goldbeter, by incorporating the role of G proteins in signal transduction. The extended model accounts for observations on the response of the signaling system to successive step increases in extracellular cAMP. In the presence of the positive feedback loop in cAMP synthesis, this model generates sustained oscillations in cAMP and in the fraction of active cAMP receptor, similar to those obtained in the simpler model where the role of the G proteins is not taken into account explicitly. We use the latter model to address the formation of concentric and spiral waves of cAMP in the course of D. discoideum aggregation. Previous analyses of the model showed that a progressive increase in the activity of adenylate cyclase and phosphodiesterase can account for the transitions no relay-relay-oscillations-relay observed in the experiments. We show that the degree of cellular synchronization on such a developmental path in parameter space markedly affects the nature of the spatial patterns generated by the model. These patterns range from concentric waves to a small number of large spirals, and finally to a large number of smaller spirals, as the degree of developmental desynchronization between cells increases.