cAMP oscillations during aggregation of Dictyostelium

For many years it has been known that developing cells of Dictyostelium discoideum show periodic surges as they aggregate. When it was discovered that the cells were responding chemotactically to cAMP gradients produced within the populations, experiments were carried out that demonstrated similar periodic changes in the concentration of extracellular cAMP. Moreover, homogenous populations of developed cells held in suspension could be shown to respond to cAMP by changes in cell shape. Such suspensions showed spontaneous oscillations in light scattering as well as cAMP levels as the result of entrainment of the cells. The molecular components necessary for the pulsatile release of cAMP were uncovered by analyzing the behavior of a large number of strains with defined mutations isolated from saturation mutagenic screens. Subsequent genetic and biochemical studies established the connections between a dozen proteins essential for spontaneous oscillations. Computer simulations of a molecular circuit based on these results showed that it is able to account for the temporal and quantitative aspects of the oscillatory system. The circuit also appears to be coupled to the construction and dismantling of the actin/myosin cortical layer that ensures that pseudopods are restricted to the anterior of cells during chemotaxis and that the cells do not back-track when the natural wave is behind them. Since the same molecular clock controls both signal production and signal response, these behaviors are always kept strictly in phase.