Inhibitory modulation of distal C-terminal on protein kinase C-dependent phospho-regulation of rat TRPV1 receptors

The Journal of Physiology
Beiying LiuFeng Qin

Abstract

The vanilloid receptor TRPV1, previously known as VR1, has been implicated in pain sensation under both physiological and pathological conditions. The channel is highly expressed in sensory ganglion neurones and is activated by a range of noxious stimuli including irritant chemicals, acids and heat. In order to understand the structural basis underlying this polymodal activation and the regulation by intracellular signalling pathways, we have investigated the functional roles of the cytoplasmic C-terminal of rat TRPV1. A mutant with the maximal truncation of the distal C-terminal encompassing the last 88 residues was constructed. Of interest, this mutant exhibited a Ca(2+)-dependent functional loss; it was irresponsive to capsaicin in the presence of extracellular Ca(2+), but fully functional otherwise. Further studies of this construct revealed that extracellular Ca(2+) alone could activate the channel, and that the activation required protein kinase C (PKC) phosphorylation at S502, an event that was up-regulated by external Ca(2+) entry. We compared the truncation mutant with wild-type TRPV1 and demonstrated that it had a significantly increased sensitivity to PKC phosphorylation. These results suggest the distal C-terminal o...Continue Reading

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Citations

Dec 23, 2009·Quarterly Reviews of Biophysics·Ramon LatorreSebastian Brauchi
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jing YaoFeng Qin
Sep 20, 2011·The Journal of Biological Chemistry·Shu Wang, Huai-hu Chuang
Sep 2, 2009·The Journal of General Physiology·Beiying LiuFeng Qin
Nov 11, 2010·Acta Physiologica·R L Baylie, J E Brayden
Oct 13, 2007·The Journal of Physiology·José A Matta, Gerard P Ahern
Dec 23, 2006·Seminars in Cell & Developmental Biology·Jiehong HuangPeter A McNaughton
Aug 16, 2005·British Journal of Pharmacology·Kathy G SuttonGuy R Seabrook
Jan 21, 2010·Molecular Nutrition & Food Research·Nadine CrouzinMichel Vignes
Dec 17, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shanshan SongJason X-J Yuan
Jan 13, 2005·Molecular Pharmacology·Gang LuSidney A Simon
Mar 14, 2007·Journal of Neurophysiology·Lieju LiuS A Simon

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