G protein-coupled receptor kinase function is essential for chemosensation in C. elegans.
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.
Fukuto
Hana S
HS
Department of Biology, University of California, San Diego, La Jolla, CA 92093 USA.
Ferkey
Denise M
DM
Apicella
Alfonso J
AJ
Lans
Hannes
H
Sharmeen
Tahira
T
Chen
Wei
W
Lefkowitz
Robert J
RJ
Jansen
Gert
G
Schafer
William R
WR
Hart
Anne C
AC
D000818:Animals; D019390:Arrestins / Q000172:deficiency / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002628:Chemoreceptor Cells / Q000166:cytology / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics; D020555:GTP-Binding Protein Regulators / Q000172:deficiency / Q000235:genetics; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000166:cytology / Q000201:enzymology*; D009475:Neurons, Afferent / Q000166:cytology / Q000201:enzymology*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051552:beta-Adrenergic Receptor Kinases
D019390:Arrestins; D029742:Caenorhabditis elegans Proteins; C120636:EAT-16 protein, C elegans; D020555:GTP-Binding Protein Regulators; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; C110666:odr-3 protein, C elegans; D010770:Phosphotransferases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go