title: [Phosphorylation-independent desensitization of metabotropic glutamate receptor 5 by G protein-coupled receptor kinase 2 in HEK 293 cells].
abstract: The metabotropic glutamate receptor 5 (mGluR5) is one of the important excitatory neurotransmitter receptors in the central nervous system, and its desensitization by G protein-coupled receptor kinases (GRKs) plays an important role in neuron protection against receptor overstimulation. It is reported that GRK2 could down-regulate the mGluR5 signaling in both HEK 293 cells and neurons. However, whether GRK2-mediated mGluR5 desensitization is phosphorylation dependent remains controversial. Here, we demonstrated that the signal intensity and kinetics of mGluRS desensitization was inhibited or changed by GRK2 in HEK 293 cells. By using the catalytically inactive GRK2 mutant K220R, and the receptor mutants that lack potential phosphorylation sites in the C-terminal tail, we demonstrated that the GRK2-mediated mGluR5 desensitization was phosphorylation-independent. Furthermore, overexpression of an N-terminal regulator of G protein signaling (RGS) homology (RH) domain of GRK2 was sufficient to attenuate the mGluR5 signaling, whereas the expression of GRK2 D110A mutant devoid in Galphaq binding was unable to inhibit mGluRS signaling. In summary, this study provides evidence that GRK2 mediates phosphorylation-independent mGluR5 desensitization via the interaction between the RGS domain and Galphaq in HEK 293 cells.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Ding
authors.forename: S
authors.initials: S
authors.lastname: Huang
mesh_terms: D002490:Central Nervous System / Q000378:metabolism*; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism
chemical_list: C578935:GRM5 protein, human; D020555:GTP-Binding Protein Regulators; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D054768:G-Protein-Coupled Receptor Kinases