PMID:15157420

Citation	Fukuto, HS, Ferkey, DM, Apicella, AJ, Lans, H, Sharmeen, T, Chen, W, Lefkowitz, RJ, Jansen, G, Schafer, WR and Hart, AC (2004) G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron 42:581-93
Abstract	G protein-coupled receptors (GPCRs) mediate diverse signaling processes, including olfaction. G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling. Despite previously described roles for GRKs in GPCR signal downregulation, animals lacking C. elegans G protein-coupled receptor kinase-2 (Ce-grk-2) function are not hypersensitive to odorants. Instead, decreased Ce-grk-2 function in adult sensory neurons profoundly disrupts chemosensation, based on both behavioral analysis and Ca(2+) imaging. Although mammalian arrestin proteins cooperate with GRKs in receptor desensitization, loss of C. elegans arrestin-1 (arr-1) does not disrupt chemosensation. Either overexpression of the C. elegans Galpha subunit odr-3 or loss of eat-16, which encodes a regulator of G protein signaling (RGS) protein, restores chemosensation in Ce-grk-2 mutants. These results demonstrate that loss of GRK function can lead to reduced GPCR signal transduction and suggest an important role for RGS proteins in the regulation of chemosensation.
Links	PubMed
Keywords	Animals; Arrestins/deficiency; Arrestins/genetics; Caenorhabditis elegans/cytology; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics; Chemoreceptor Cells/cytology; Chemoreceptor Cells/enzymology; Cyclic AMP-Dependent Protein Kinases/deficiency; Cyclic AMP-Dependent Protein Kinases/genetics; GTP-Binding Protein Regulators/deficiency; GTP-Binding Protein Regulators/genetics; GTP-Binding Protein alpha Subunits, Gi-Go/deficiency; GTP-Binding Protein alpha Subunits, Gi-Go/genetics; Gene Expression Regulation, Enzymologic/genetics; Mutation/genetics; Nervous System/cytology; Nervous System/enzymology; Neurons, Afferent/cytology; Neurons, Afferent/enzymology; Phosphoproteins/deficiency; Phosphoproteins/genetics; Phosphotransferases/genetics; Phosphotransferases/metabolism; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism; Signal Transduction/genetics; beta-Adrenergic Receptor Kinases
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