TY - JOUR
T1 - cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation
AU - Bhave, Gautam
AU - Zhu, Weiguo
AU - Wang, Haibin
AU - Brasier, D. J.
AU - Oxford, Gerry S.
AU - Gereau IV, Robert W.
N1 - Funding Information:
We would like to thank Dr. Richard Cook and the Baylor College of Medicine Protein Sequencing Core Facility for assistance with Edman sequencing and mass spectroscopy. We would also like to thank Sheetal Mehta for assistance with tissue culture. We acknowledge Dr. David Julius for kindly providing rat VR1 cDNA. This work was supported by grants from the National Institutes of Health (R01MH60230 and R01NS42595 to R.W.G. and R01NS18788 and P01NS39420 to G.S.O). G.B. is a McNair Scholar of the Baylor College of Medicine Medical Scientist Training Program.
PY - 2002/8/15
Y1 - 2002/8/15
N2 - The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.
AB - The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.
UR - http://www.scopus.com/inward/record.url?scp=0037104657&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(02)00802-4
DO - 10.1016/S0896-6273(02)00802-4
M3 - Article
C2 - 12194871
AN - SCOPUS:0037104657
SN - 0896-6273
VL - 35
SP - 721
EP - 731
JO - Neuron
JF - Neuron
IS - 4
ER -