J Biol Chem. 2010 May 14;285(20):15167-77. Epub 2010 Mar 15.

Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel.External

Staruschenko, A., Jeske, N. A., Akopian, A. N.,
["Department of Physiology and Kidney Disease Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-0509, USA."]
Several lines of evidence suggest that TRPA1 and TRPV1 mutually control the transduction of inflammation-induced noxious stimuli in sensory neurons. It was recently shown that certain TRPA1 properties are modulated by TRPV1. However, direct interaction between TRPA1 and TRPV1 as well as regulation of TRPA1 intrinsic characteristics by the TRPV1 channel have not been examined. To address these questions, we have studied a complex formation between TRPA1 and TRPV1 and characterized the influence of TRPV1 on single channel TRPA1-mediated currents. Co-immunoprecipitation analysis revealed direct interactions between TRPA1 and TRPV1 in an expression system as well as in sensory neurons. Data generated with total internal reflection fluorescence-based fluorescence resonance energy transfer indicate that a TRPA1-TRPV1 complex can be formed on the plasma membrane. The fluorescence resonance energy transfer interaction between TRPA1 and TRPV1 channels is as effective as for TRPV1 or TRPA1 homomers. Single channel analysis in a heterologous expression system and in sensory neurons of wild type and TRPV1 knock-out mice demonstrated that co-expression of TRPV1 with TRPA1 results in outward rectification of single channel mustard oil (I(MO)) current-voltage relationships (I-V) and substantial modulation of the open probability at negative holding potentials. TRPV1 also does not influence the characteristics of single channel I(MO) in Ca(2+)-free extracellular solution. However, association of TRPA1 with TRPV1 was not affected in Ca(2+)-free media. To assess a role of intracellular Ca(2+) in TRPV1-dependent modulation of TRPA1 modulation, the TRPA1-mediated single channel WIN55,212-2-gated current (I(WIN)) was recorded in inside-out configuration. Our data indicate that single channel properties of TRPA1 are regulated by TRPV1 independently of intracellular Ca(2+). In summary, our results support the hypothesis that TRPV1 and TRPA1 form a complex and that TRPV1 influences intrinsic characteristics of the TRPA1 channel.
PMID: 20231274External
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 TRPV1 Inference Prediction 20231274
TRPV1 Link TRPA1 Inference Prediction 20231274
(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 TRPV1 Co-immunoprecipitation CHO Mouse Full-length Rat Full-length 20231274
TRPA1 Link TRPV1 Co-immunoprecipitation Mouse trigeminal ganglia lysates 20231274
TRPV1 Link TRPA1 Co-immunoprecipitation CHO Rat Full-length Mouse Full-length 20231274
TRPV1 Link TRPA1 Co-immunoprecipitation Mouse trigeminal ganglia lysates 20231274
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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