1. The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive behavioral sensitivity.
- Author
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Krzyzanowski MC, Brueggemann C, Ezak MJ, Wood JF, Michaels KL, Jackson CA, Juang BT, Collins KD, Yu MC, L'etoile ND, and Ferkey DM
- Subjects
- Animals, Caenorhabditis elegans physiology, Caenorhabditis elegans Proteins metabolism, 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, Behavior, Animal physiology, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Cyclic GMP metabolism, Cyclic GMP-Dependent Protein Kinases genetics
- Abstract
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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
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