The C. elegans cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity

Michelle C. Krzyzanowski, Chantal Brueggemann, Meredith J. Ezak, Jordan F. Wood, Kerry L. Michaels, Christopher A. Jackson, Bi-Tzen Juang, Kimberly D. Collins, Michael C. Yu, Noelle D. L'Etoile, Denise M. Ferkey

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish
Article numbere1003619
JournalPLoS Genetics
Issue number7
StatePublished - 1 Jul 2013

Fingerprint Dive into the research topics of 'The C. elegans cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity'. Together they form a unique fingerprint.

Cite this