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NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels
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Zhang, Xuming, Huang, Jiehong and McNaughton, Peter A. (2005) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. The EMBO Journal, 24 (24). pp. 4211-4223. doi:10.1038/sj.emboj.7600893 ISSN 0261-4189.
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Official URL: http://dx.doi.org/10.1038/sj.emboj.7600893
Abstract
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.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | The EMBO Journal | ||||
Publisher: | Nature Publishing Group | ||||
ISSN: | 0261-4189 | ||||
Official Date: | 21 December 2005 | ||||
Dates: |
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Volume: | 24 | ||||
Number: | 24 | ||||
Page Range: | pp. 4211-4223 | ||||
DOI: | 10.1038/sj.emboj.7600893 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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