The C. elegans cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity |
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| Authors: | 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 |
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| Affiliation: | 1.Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America;2.Department of Cell and Tissue Biology, University of California, San Francisco, California, United States of America;Stanford University School of Medicine, United States of America |
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| 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. |
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