Journal
EMBO JOURNAL
Volume 24, Issue 24, Pages 4211-4223Publisher
WILEY
DOI: 10.1038/sj.emboj.7600893
Keywords
membrane trafficking; neurotrophic factor; pain; sensory transduction; tyrosine kinase
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/C003217/1] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/C003217/1] Funding Source: Medline
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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.
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