title: The basal thermal sensitivity of the TRPV1 ion channel is determined by PKCβII.
abstract: Peripheral nociceptors are excited by the activation of membrane receptors and ion channels. The heat-sensitive TRPV1 ion channel responds to various noxious chemical and thermal stimuli, causing pain and itch. Here, we show that TRPV1 is coexpressed with PKCβII in a subset of mouse sensory neurons and that, in these neurons, TRPV1 binds directly to PKCβII, leading to the activation and translocation of PKCβII. Activated PKCβII, in turn, significantly increases the responsiveness of TRPV1 by phosphorylating Thr705. The heat sensitivity of TRPV1 is almost eliminated by either knocking down PKCβII or mutating Thr705; however, neither of these manipulations affects the potentiation of TRPV1 caused by the activation of PKCε. PKCβII thus acts as an auxiliary subunit of TRPV1 by forming a population-dependent TRPV1 ion channel complex controlling the sensitivity of TRPV1 and setting the threshold for pain and itch.
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, United Kingdom, and.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, United Kingdom, and Rowett Institute of Nutrition and Health and Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Raquibul
authors.initials: R
authors.lastname: Hasan
authors.affiliation: Rowett Institute of Nutrition and Health and Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom x.zhang@abdn.ac.uk.
authors.forename: Xuming
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D064546:Protein Kinase C beta / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D049452:Green Fluorescent Proteins; D064546:Protein Kinase C beta; D002211:Capsaicin
keywords: PKC; TRP ion channels; TRPV1; auxiliary subunit; pain; phosphorylation