GrlJ, a Dictyostelium GABA(B)-like receptor with roles in post-aggregation development

BACKGROUND: The G-protein-coupled receptor (GPCR) family represents the largest and most important group of targets for chemotherapeutics. They are extremely versatile receptors that transduce signals as diverse as biogenic amines, purins, odorants, ions and pheromones from the extracellular compartment to the interior via biochemical processes involving GTP-binding proteins. Until recently, the cyclic AMP receptors (cARs) were the only known G protein coupled receptors in Dictyostelium discoideum. The completed genome sequence revealed the presence of several families of GPCRs in Dictyostelium, among them members of the family 3 of GPCRs, the GABA(B)/glutamate like receptor family, which in higher eukaryotes is involved in neuronal signaling. RESULTS: D. discoideum has seventeen Family 3 members of GPCRs, denoted GrlA through GrlR. Their transcripts are detected throughout development with increased levels during early and late development. We have examined here GrlJ. GFP-tagged GrlJ localises to the plasmamembrane and to internal membranes. Inactivation of the grlJ gene leads to precocious development, and the mutant completes development ~6 hours earlier. Alterations were also noted at the slug stage and in spore formation. grlJ(- )slugs were longer and broke apart several times on their way to culmination forming smaller but proportionate fruiting bodies. Spores from grlJ(- )fruiting bodies were malformed and less viable, although the spore differentiation factors were synthesized and sensed normally. Expression of a GFP-tagged full length GrlJ rescued the phenotype. CONCLUSION: Our data suggest that GrlJ acts at several stages of Dictyostelium development and that it is a negative regulator in Dictyostelium development.