Abstract
BackgroundThe 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 GABAB/glutamate like receptor family, which in higher eukaryotes is involved in neuronal signaling.ResultsD. 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.ConclusionOur data suggest that GrlJ acts at several stages of Dictyostelium development and that it is a negative regulator in Dictyostelium development.
Highlights
The G-protein-coupled receptor (GPCR) family represents the largest and most important group of targets for chemotherapeutics
Our data suggest that GrlJ acts at several stages of Dictyostelium development and that it is a negative regulator in Dictyostelium development
Most of them have a signalpeptide and a BMP domain in their amino terminal region, a domain which was first found in outer membrane proteins of bacteria, and which is similar to the Venus Flytrap module (VFTM) that forms the ligand binding site in the N-termini of metabotropic GPCRs [8]
Summary
The G-protein-coupled receptor (GPCR) family represents the largest and most important group of targets for chemotherapeutics. The seven-transmembrane spanning G protein-coupled receptors (GPCRs) represent a major group of cell-surface detectors and constitute 3.5 % of the genome in vertebrates [1] They play a key role in the physiology of multicellular organisms as they transduce a broad variety of extracellular signals into the cell. Several other signaling molecules such as cell density factors, folate and related pterins, LPA (lysophosphatidic acid), PSF (prestarvation factor), CF (conditioned media factor), small metabolites and numerous small peptides are known to be acting via GPCRs as well [4,5]. Their receptors have not been identified so far
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