Evolutional Divergence of the Metabotropic Glutamate Receptor Genes: A New Receptor Belonging to the Metabotropic Glutamate Receptor Family in Dictyostelium discoideum

Glutamate receptors are the principal neurotransmitter receptors in the central nervous system and categorized into ionotopic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). iGluRs internally contain ligand-gated ion-channels, and mGluRs are a class of G-protein coupled receptors (GPCRs) that possess a seven transmembrane region. iGluRs are considered to diverge as ligand-gated channel proteins from ancestral potassium channels. A prokaryotic iGluR, GluR0, has been found to bind glutamate, form potassium-selective channels and be related in amino-acid sequence to both eukaryotic iGluRs and potassium channels. While, the class III GPCRs including the sensory receptors, the GABAβ receptors (GABAβRs) and mGluRs are considered to diverge from common ancestral GPCRs. mGluR orthologs have been identified in Drosophila, C. elegans and higher organisms. We have screened the Dictyostelium genome database using ligand binding domain of rat mGluR1 as a bait, and identified a receptor, DdmGluPR (Dictyostelium metabotropic glutamate precursor receptor), belonging to the mGluR family. The residues of mGluRs involved in the binding of the α-carboxylic and α-amino groups of glutamate are well conserved in DdmGluPR but the residues interacting with the γ-carboxylic group of glutamate are not. The phylogenetic analysis suggests that DdmGluPR diverged after the mGluR family-GABAβ receptors split but before mGluR family divergence. GABA induces but glutamate acts as a competitive inhibitor of GABA for the efficient induction of encapsulation through DdmGluPR in Dictyostelium. DdmGluPR has a hybrid structure with extracellular region similar to mGluRs and transmembrane region similar to GABAβRs. We propose that DdmGluPR is evolutionary precursor to mGluRs.