Cyclic GMP in Dictyostelium discoideum Oscillations and pulses in response to folic acid and cyclic AMP signals

Abstract

Cells of Dictyostelium discoideum respond chemotactically to.cyclic AMP [l] and to folic acid [3]. Cyclic AMP is a most efficient attractant for cells of the aggregation phase [2], folic acid is more effective with preaggregation cells [4]. Both cyclic AMP and folic acid stimulate also cell development from the preaggregation phase to the aggregation competent state [S-8]. During this process the cells acquire the capacity to synthesize cyclic AMP periodically, and to release it into the extracellular space in form of pulses [9] . The administration of cyclic AMP or folic acid pulses accelerates the onset of sustained oscillations [5,8] .The cyclic-AMP induced responses are known to be mediated by cell-surface receptors [lo-121. The intermediate steps in signal processing from the receptors to the various intracellular targets are unknown. In the present communication we show that upon stimulation of early preaggregation cells with folic acid a rapid increase of the cyclic GMP concentration is induced. A biphasic increase of cyclic GMP is observed in late preaggregation cells stimulated by cyclic AMP. The second cyclic GMP peak is succeeded by a cyclic AMP peak known to be based on the activation of adenylate cyclase [ 131. Free-running oscillations of cyclic GMP were observed together with the periodic formation of cyclic AMP pulses, and the cyclic GMP peaks seemed to occur slightly in advance of the cyclic AMP peaks.

Cyclic AMP and folic acid mediated cyclic GMP accumulation in Dictyostelium discoideum

“…Which form of phosphodiesterase plays the most important role in controlling the cGMP content in intact cells is not known. These results indicate a role of cGMP during chemotaxis in D. discoideum, cAMP and frolic acid not only induce chemotaxis [2,3] but also cell differentiation [25][26][27] and, in the case of cAMP, adenylate cyclase activation [28]. More information is required to know which of these biological effects are regulated by cGMP.…”

Protein and phospholipid methylation during chemotaxis in Dictyostelium discoideum and its relationship to calcium movements.

“…ADP supported 38% of the activity of ATP. cAMP and cyclic GMP, which seems to be involved in the transduction of a chemotactic signal in D. discoideum (9,17), also had no effect on Ca2+ uptake. The mitochondrial uncouplers, 2,4-dinitrophenol (0.1 mM), NaN3 (0.1 mM), oligomycin (0.7,gg/ml), and ruthenium red (3 nmol/mg of protein, inhibited Ca2+ uptake by not more than 10%.…”

The G alpha subunit G alpha 4 couples to pterin receptors and identifies a signaling pathway that is essential for multicellular development in Dictyostelium.

“…Pan et al (11) identified the chemotactic agent as folic acid. The addition of folate during early development results in the activation of guanylyl and adenylyl cyclases, the rapid association of actin with the cytoskeleton, and chemotactic movement, similar to responses that are elicited by cAMP during aggregation (12)(13)(14). Tillinghast and Newell (14) showed that vegetative cells and mound-stage cells differentially exhibit chemotaxis to different folate analogues, suggesting the presence of more than one class of folate receptor (FAR).…”