Neuron. 2008 Aug 14;59(3):450-61.

Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150.External

Zhang, X., Li, L., McNaughton, P. A.,
["Department of Pharmacology, University of Cambridge, Cambridge CB21PD, UK."]
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 PGE(2) is abrogated. AKAP79/150 is therefore a final common element in heat hyperalgesia, on which the effects of multiple proinflammatory mediators converge.
PMID: 18701070External
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Screening Toggle
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPA1 Link AKAP-5 Speculation Prediction 18701070
TRPM8 Link AKAP-5 Speculation Prediction 18701070
TRPV2 Link AKAP-5 Speculation Prediction 18701070
TRPV3 Link AKAP-5 Speculation Prediction 18701070
TRPV4 Link AKAP-5 Speculation Prediction 18701070
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Validation: In vitro validation Toggle
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPV1 Link AKAP-5 Fusion protein-pull down assay Human 681-839 E. coli Not used HEK293 lysates 18701070
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Validation: In vivo validation Toggle
  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
TRPA1 Link AKAP-5 Co-immunoprecipitation HEK293 Mouse Full-length Not used 18701070
TRPM8 Link AKAP-5 Co-immunoprecipitation HEK293 Rat Full-length Not used 18701070
TRPV1 Link AKAP-5 Co-immunofluorescence staining Rat dorsal root ganglion neuron 18701070
TRPV1 Link AKAP-5 Co-immunoprecipitation Rat dorsal root ganglion neuron 18701070
TRPV1 Link AKAP-5 Co-immunoprecipitation HEK293 Human Full-length Not used 18701070
TRPV2 Link AKAP-5 Co-immunoprecipitation HEK293 Human Full-length Not used 18701070
TRPV3 Link AKAP-5 Co-immunoprecipitation HEK293 Mouse Full-length Not used 18701070
TRPV4 Link AKAP-5 Co-immunoprecipitation HEK293 Human Full-length Not used 18701070
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Characterization Toggle
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPV1 Link AKAP-5 Fusion protein-pull down assay Human 736-749 Human Not determined 18701070
TRPV1 Link AKAP-5 Co-immunoprecipitation Human 736-749 Human Not determined 18701070
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Functional consequence Toggle
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV1 Link AKAP-5 Cell surface biotinylation Increase in plasma membrane level 18701070
TRPV1 Link AKAP-5 Patch clamp Activation 18701070
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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