MODELING OSCILLATIONS AND WAVES OF CAMP IN DICTYOSTELIUM-DISCOIDEUM CELLS

We examine the theoretical aspects of temporal and spatiotemporal orga nization in the cAMP signaling system of Dictyostelium discoideum amoe bae which aggregate in a wavelike manner after starvation, in response to pulses of cAMP emitted with a periodicity of several minutes by ce lls behaving as aggregation centers. We first extend the model based o n receptor desensitization, previously proposed by Martiel and Goldbet er, by incorporating the role of G proteins in signal transduction. Th e extended model accounts for observations on the response of the sign aling system to successive step increases in extracellular cAMP. In th e presence of the positive feedback loop in cAMP synthesis, this model generates sustained oscillations in cAMP and in the fraction of activ e cAMP receptor, similar to those obtained in the simpler model where the role of the G proteins is not taken into account explicitly. We us e the latter model to address the formation of concentric and spiral w aves of cAMP in the course of D. discoideum aggregation. Previous anal yses of the model showed that a progressive increase in the activity o f adenylate cyclase and phosphodiesterase can account for the transiti ons no relay-relay-oscillations-relay observed in the experiments. We show that the degree of cellular synchronization on such a development al 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 numbe r of smaller spirals, as the degree of developmental desynchronization between cells increases. (C) 1998 Elsevier Science Ireland B.V. All r ights reserved.