G-protein-mediated interconversions of cell-surface cAMP receptors and their involvement in excitation and desensitization of guanylate cyclase in Dictyostelium discoideum.

Biased Random Walk by Stochastic Fluctuations of Chemoattractant-Receptor Interactions at the Lower Limit of Detection

“…In addition, a very short lifetime t R of the cAMPreceptor complex will lead to a lower affinity of the receptor for cAMP, which reduces the sensitivity to detect low chemoattractant concentrations. Different kinetic forms of the receptor have been observed, for which the lifetimes t R of the active receptor have been obtained between 0.7 and 3.5 s (25,26). We derived the experimental value for sampling fold I ¼ 1.8.…”

“…In Dictyostelium, the average lifetime of the cAMPreceptor complex t R is ;0.7-3.5 seconds (25,26); similar data have been obtained for the interaction between the fMLP and its receptor on human neutrophils, showing fMLP-receptor lifetimes between 0.5 and 3 s (38,39). Thus, the observed parameters for Dictyostelium are I ¼ 1.8 (range 1.2-2.4) and t R ¼ 0.7-3.5 s, which yield a hypothetical second messenger with a lifetime of t M ¼ 1.5-7 s and a diffusion rate constant of D M ¼ 0.25-4 mm 2 /s.…”

Signal transduction in Dictyostelium fgd A mutants with a defective interaction between surface cAMP receptors and a GTP-binding regulatory protein [published erratum appears in J Cell Biol 1988 Dec;107(6 Pt 1):following 2463]

“…Extracellular cAMP is detected by specific cell surface receptors, which have been subdivided in two classes, A-and B-sites, that are probably coupled to the activation of adenylate and guanylate cyclase, respectively (7,17). Binding of cAMP to both subclasses is complex and reveals in each class different forms that interconvert after stimulation of cells with cAMP (19,20). The A-sites are fast dissociating (t,/2 = 2 s) and may exist in two states (A r~ and A L) with high and low affinity, while the B-sites are slow dissociating and may exist in at least two states (B s and B ss) which release bound cAMP with t,/, = 15 and 150 s, respectively.…”

“…Several observations point to a role of G-proteins in transmembrane signal transduction in D. discoideum. Guanine nucleotides alter the heterogeneity of cAMP binding to isolated membranes, suggesting the interaction of G-protein(s) with cAMP receptors (16,20). [3H]GTP or [35S]GTP3,Sbinding to D. discoideum membranes and its potentiation by cAMP also point to a functional coupling between cell surface receptors and G-proteins (3,13).…”

Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

“…It was shown, for instance, that in the rat cerebral cortex Li + also interferes with the function of G-proteins (Avissar et al 1988). The observed LiClinduced increase of cyclic AMP binding activity could reflect an effect on G-proteins, since the functional interaction between cyclic AMP receptors and G-proteins involves changes in receptor affinity (Janssens et al 1986;Van Haastert et al 1986). The identity of the target for the effect of L i + on CP-2 expression will be further investigated.…”