J Neurosci. 2014 Jun 11;34(24):8246-58. doi: 10.1523/JNEUROSCI.0278-14.2014.

The basal thermal sensitivity of the TRPV1 ion channel is determined by PKCbetaII.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Li, L., Hasan, R., Zhang, X.,
["Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, United Kingdom, and.", "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.", "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."]
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 PKCbetaII in a subset of mouse sensory neurons and that, in these neurons, TRPV1 binds directly to PKCbetaII, leading to the activation and translocation of PKCbetaII. Activated PKCbetaII, in turn, significantly increases the responsiveness of TRPV1 by phosphorylating Thr705. The heat sensitivity of TRPV1 is almost eliminated by either knocking down PKCbetaII or mutating Thr705; however, neither of these manipulations affects the potentiation of TRPV1 caused by the activation of PKCepsilon. PKCbetaII 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.
PMID: 24920628External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Inference Prediction 24920628
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Co-immunofluorescence staining HEK293 Human Full-length Human Full-length 24920628
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Co-immunofluorescence staining Rat dorsal root ganglion cell 24920628
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Co-immunoprecipitation Rat dorsal root ganglion cell 24920628
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Co-immunoprecipitation HEK293 Human Full-length Human Full-length 24920628
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Characterization Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Fusion protein-pull down assay Human 1-433 Human 341-673 24920628
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ In vivo PTM assay Phosphorylation (Thr-705) 24920628
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKCƢ Patch clamp Activation 24920628
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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