NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels

Xuming Zhang, Jiehong Huang, Peter A McNaughton

Research output: Contribution to journalArticle

496 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4211-23
Number of pages13
JournalEMBO Journal
Volume24
Issue number24
DOIs
Publication statusPublished - 21 Dec 2005

Keywords

  • Amino Acid Sequence
  • Animals
  • Calcium
  • Capsaicin
  • Cell Line
  • Cells, Cultured
  • DNA
  • DNA, Complementary
  • Electrophysiology
  • Gene Expression Regulation
  • Glutathione Transferase
  • Hot Temperature
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Ion Channels
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Nerve Growth Factor
  • Neurons
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Plasmids
  • Protein Binding
  • Receptor, trkA
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Sodium
  • TRPV Cation Channels
  • Time Factors
  • Transfection
  • Tyrosine
  • Vanadates
  • src-Family Kinases

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