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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


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.




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



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

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