The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive behavioral sensitivity

PLoS Genet. 2013;9(7):e1003619. doi: 10.1371/journal.pgen.1003619. Epub 2013 Jul 11.


Signaling levels within sensory neurons must be tightly regulated to allow cells to integrate information from multiple signaling inputs and to respond to new stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4 in the negative regulation of G protein-coupled nociceptive chemosensory signaling. C. elegans lacking EGL-4 function are hypersensitive in their behavioral response to low concentrations of the bitter tastant quinine and exhibit an elevated calcium flux in the ASH sensory neurons in response to quinine. We provide the first direct evidence for cGMP/PKG function in ASH and propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4 dampens quinine sensitivity via phosphorylation and activation of the regulator of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate Gα signaling and behavioral sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / genetics*
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Phosphorylation
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology
  • Signal Transduction / genetics


  • Caenorhabditis elegans Proteins
  • RGS Proteins
  • Cyclic GMP-Dependent Protein Kinases
  • EGL-4 protein, C elegans
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Cyclic GMP