G protein-coupled receptor kinase function is essential for chemosensation in C. elegans

Neuron. 2004 May 27;42(4):581-93. doi: 10.1016/s0896-6273(04)00252-1.


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


  • 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