Abstract
Metabotropic glutamate receptors (mGluRs) are a class of G-protein-coupled receptors that possess a seven transmembrane region involved in the modulation of excitatory synaptic transmission in the nervous system. mGluR orthologs have been identified in Drosophila, Caenorhabditis elegans, and higher organisms. Drosophila possesses two mGluR genes, DmGluRA and DmXR. We screened the Dictyostelium genome data base using the ligand binding domain of rat mGluR1 as bait, and identified a new receptor, DdmGluPR, belonging to the mGluR family. Similar to Drosophila DmXR, the residues of mGluRs involved in the binding of the alpha-carboxylic and alpha-amino groups of glutamate were well conserved in DdmGluPR, but the residues interacting with the gamma-carboxylic group of glutamate were not. The phylogenetic analysis suggests that DdmGluPR diverged after the mGluR family-GABA(B) receptors split but before mGluR family divergence. DdmGluPR mRNA was expressed in vegetative cells and throughout starvation-induced development, but the level of the expression was relatively high until 4 h after starvation. DdmGluPR was localized to the plasma membrane of axenically grown Ax-2 cells expressed as a green fluorescent protein fusion protein. DdmGluPR-null cells grew faster at high cell density and reached higher densities than wild-type cells. DdmGluPR-null cells exhibited delayed aggregates formation upon starvation and impaired chemotaxis toward cAMP. Although expressions of cAR1 and aca, cAMP-signaling components, were rapidly induced and peaked at 2-4 h in wild-type cells, DdmGluPR-null cells displayed sustained and peaked at 8 h of the expressions of these genes. Our findings suggest the involvement of DdmGluPR in the early development of Dictyostelium discoideum.
Highlights
Ilarity, agonist selectivity, and effector system differences: subgroup I, subgroup II, and subgroup III [1]
Because DdmGluPR has a hybrid structure with an extracellular region similar to Metabotropic glutamate receptors (mGluRs) and a transmembrane region similar to GABAB receptors (GABABRs), we propose that DdmGluPR was the evolutionary precursor to mGluRs
Glutamate receptors are categorized into ionotropic glutamate receptors and mGluRs
Summary
Ilarity, agonist selectivity, and effector system differences: subgroup I (mGluR1 and -5), subgroup II (mGluR2 and -3), and subgroup III (mGluR4, -6, -7, and -8) [1]. The extracellular region is further divided into the ligand binding domain (LBD) and the cysteine-rich region They share sequence similarity with the calcium-sensing receptor [3] and the pheromone receptor [4, 5] to form the mGluR family. A sequence analysis of the LBD of Drosophila DmXR revels that the residues contacting the amino acid moiety of glutamate are conserved, whereas the residues interacting with the ␥-carboxylic group are not. Cells differentiate to specific cell types and culminate into a fruiting body consisting of spores on top of a supporting stalk During this process, extracellular cAMP signaling and cAMP-specific GPCRs are involved in its multicellular development. A sequence comparison between DdmGluPR and mGluRs revealed that only part of the residues involved in the glutamate binding was conserved like Drosophila DmXR. A mGluR Gene in Dictyostelium important roles of the DdmGluPR gene in aggregates formation during Dictyostelium development
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