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Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150
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Zhang, Xuming, Li, Lin and McNaughton, Peter A. (2008) Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron, 59 (3). pp. 450-461. doi:10.1016/j.neuron.2008.05.015 ISSN 0896-6273.
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Official URL: http://dx.doi.org/10.1016/j.neuron.2008.05.015
Abstract
The ability of vertebrates to detect and avoid damaging extremes of temperature depends on activation of ion channels belonging to the thermo-TRP family. Injury or inflammation causes the release of inflammatory mediators which lower the threshold for detection of painful levels of heat, a process known as heat hyperalgesia. These inflammatory mediators act by at least three distinct intracellular signaling pathways. Here, we show that modulation of the sensitivity of the heat-activated ion channel TRPV1 by the protein kinases PKA and PKC and by the phosphatase calcineurin depends on the formation of a signaling complex between these enzymes, the scaffolding protein AKAP79/150 and TRPV1. We identify a critical region in the TRPV1 C-terminal which mediates binding of AKAP79/150. If binding is prevented, then sensitization by both bradykinin and PGE2 is abrogated. AKAP79/150 is therefore a final common element in heat hyperalgesia, on which the effects of multiple proinflammatory mediators converge.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Neuron | ||||
Publisher: | Cell Press | ||||
ISSN: | 0896-6273 | ||||
Official Date: | 14 August 2008 | ||||
Dates: |
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Volume: | 59 | ||||
Number: | 3 | ||||
Page Range: | pp. 450-461 | ||||
DOI: | 10.1016/j.neuron.2008.05.015 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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