Adenylate cyclase activity oscillations as signals for cell aggregation in Dictyostelium discoideum

Abstract

As well as acting as a chemotactic factor1 cyclic AMP stimulates cells of Dictyostelium discoideum to differentiate after the end of growth into aggregation-competent cells. These differentiation signals have a temporal pattern : pulses are efficient signals, whereas continuous administration of cyclic AMP may even have an adverse effect2,3. D. discoideum cells can release cyclic AMP spontaneously as reiterated pulses4, and also release cyclic AMP in response to extraneous cyclic AMP pulses5–7, which is important for the transmission of signals in aggregation territories in form of propagated waves8–12. The pulsatile release of cyclic AMP into the extracellular space is preceded by a sharp (about 10-fold) increase of its intracellular concentration within 1 min (ref. 4). This indicates that the oscillating variable is not only transport but also net synthesis of cyclic AMP. The periodic rise of the intracellular cyclic AMP concentration could be due to periodic activation of adenylate cyclase, to inhibition of phosphodiesterase, or to the oscillatory control of both enzymes. We present here evidence for sustained oscillations of the adenylate cyclase activity in signalling cells. No concomitant changes of the ATP concentration, the substrate of adenylate cyclase, were found.