Secretion of cyclic AMP induced by cyclic AMP in the cellular slime mould Dictyostelium discoideum

Abstract

A STRIKING feature of aggregation in large species of Dictyostelium is the appearance of repeated waves of centripetal movement propagated outwards from the centres1,2. I accounted for them as follows3–8. The cells are not only oriented by the chemotactic agent, acrasin9, but induced to secrete it; they thus relay the orienting signals. The detailed aggregation pattern, before contact modifies it, records the transmission of these signals. To avoid an infinite regress, some secreted factor must induce its own secretion; this was tentatively assumed to be the attractant itself. There would then be separate thresholds for attraction and secretion. The dual responsiveness develops during the preaggregation phase. Aggregation centres are started by the first cells to secrete signals supraliminal for their neighbours. That separate cells, having oriented to the signal and transmitted it outwards, do not reorient to the signal now coming from behind them and transmit it centripetally, was ascribed to some combination of reduced receptor, motor, and secretory activities, expressed as an absolute or relative refractory period, and to changes in cell shape, spacing, orientation, and polarity, once the cells have responded. The precise signal profile may be significant. After an interval, the cells can transmit a new pulse in any direction. Commonly the same cells as before initiate the later pulses and thus remain dominant, but pulses from other pacemakers can recruit and reorient those cells they reach first. Secreted acrasin is rapidly inactivated enzymically. It was argued that this is functionally useful in maintaining the detectability of the signal even with a single source, and vastly more so with literally millions of sources. Enzymic breakdown could also yield a metabolite for recycling. Later work10–12 has very largely confirmed this. The attractant in D. discoideum is cyclic AMP13, and the inactivating enzymes phosphodiesterases (PDE)14–16. Cyclic AMP pulsed from a microelectrode induces propagated waves of movement17. A mathematical model has incorporated most of the above features18. The present work demonstrates directly that cyclic AMP does induce aggregating cells to secrete cyclic AMP.