EMBO J. 2005 Dec 21;24(24):4211-23. Epub 2005 Dec 1.

NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Zhang, X., Huang, J., McNaughton, P. A.,
["Department of Pharmacology, University of Cambridge, Cambridge, UK."]
Nociceptors, or pain-sensitive receptors, are unique among sensory receptors in that their sensitivity is increased by noxious stimulation. This process, called sensitization or hyperalgesia, is mediated by a variety of proinflammatory factors, including bradykinin, ATP and NGF, which cause sensitization to noxious heat stimuli by enhancing the membrane current carried by the heat- and capsaicin-gated ion channel, TRPV1. Several different mechanisms for sensitization of TRPV1 have been proposed. Here we show that NGF, acting on the TrkA receptor, activates a signalling pathway in which PI3 kinase plays a crucial early role, with Src kinase as the downstream element which binds to and phosphorylates TRPV1. Phosphorylation of TRPV1 at a single tyrosine residue, Y200, followed by insertion of TRPV1 channels into the surface membrane, explains most of the rapid sensitizing actions of NGF.
PMID: 16319926External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
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 SRC Co-immunoprecipitation HEK293 16319926
(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 SRC Fusion protein-pull down assay Human 1-433 Rat 83-144 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SRC Fusion protein-pull down assay Human 681-839 Rat 83-144 16319926
(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 SRC In vitro PTM assay Phosphorylayion (Tyr-200) 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SRC In vivo PTM assay Phosphorylayion (Tyr-200) 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SRC Calcium measurement Activation 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SRC Patch clamp Activation 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TrkA In vivo PTM assay Phosphorylayion (Tyr-200) 16319926
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TrkA Patch clamp Activation 16319926
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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