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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
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
Substances
-
Arrestins
-
Caenorhabditis elegans Proteins
-
EAT-16 protein, C elegans
-
GTP-Binding Protein Regulators
-
Phosphoproteins
-
Receptors, G-Protein-Coupled
-
odr-3 protein, C elegans
-
Phosphotransferases
-
Cyclic AMP-Dependent Protein Kinases
-
beta-Adrenergic Receptor Kinases
-
GTP-Binding Protein alpha Subunits, Gi-Go