J Neurosci. 2010 Oct 6;30(40):13338-47. doi: 10.1523/JNEUROSCI.2108-10.2010.
Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate.
Mercado, J., Gordon-Shaag, A., Zagotta, W. N., Gordon, S. E.,
["Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA."]
["Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA."]
TRPV2 is a member of the transient receptor potential family of ion channels involved in chemical and thermal pain transduction. Unlike the related TRPV1 channel, TRPV2 does not appear to bind either calmodulin or ATP in its N-terminal ankyrin repeat domain. In addition, it does not contain a calmodulin-binding site in the distal C-terminal region, as has been proposed for TRPV1. We have found that TRPV2 channels transiently expressed in F-11 cells undergo Ca(2+)-dependent desensitization, similar to the other TRPVs, suggesting that the mechanism of desensitization may be conserved in the subfamily of TRPV channels. TRPV2 desensitization was not altered in whole-cell recordings in the presence of calmodulin inhibitors or on coexpression of mutant calmodulin but was sensitive to changes in membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)), suggesting a role of membrane PIP(2) in TRPV2 desensitization. Simultaneous confocal imaging and electrophysiological recording of cells expressing TRPV2 and a fluorescent PIP(2)-binding probe demonstrated that TRPV2 desensitization was concomitant with depletion of PIP(2). We conclude that the decrease in PIP(2) levels on channel activation underlies a major component of Ca(2+)-dependent desensitization of TRPV2 and may play a similar role in other TRP channels.
PMID: 20926660

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Validation: In vitro validation
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Assay with recombinant proteins | Reference | |||||||||
TRP channel construct | Interactor construct | |||||||||
TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
TRPV2 |
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Calmodulin | Fusion protein-pull down assay | Rat | 684-753 | Not specified | Not determined | Not specified | E. coli | 20926660 |
TRPV3 |
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Calmodulin | Fusion protein-pull down assay | Mouse | ARD domain | Not specified | Not determined | Not specified | In vitro translation | 20926660 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Characterization
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Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPV1 |
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Calmodulin | Fusion protein-pull down assay | Rat | ARD domain | Not specified | Not determined | 20926660 | ||
TRPV2 |
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Calmodulin | Fusion protein-pull down assay | Rat | 684-753 | Not specified | Not determined | 20926660 | ||
TRPV3 |
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Calmodulin | Fusion protein-pull down assay | Mouse | ARD domain | Not specified | Not determined | 20926660 | ||
TRPV4 |
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Calmodulin | Fusion protein-pull down assay | Rat | ARD domain | Not specified | Not determined | 20926660 | ||
TRPV5 |
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Calmodulin | Fusion protein-pull down assay | Human | ARD domain | Not specified | Not determined | 20926660 | ||
TRPV6 |
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Calmodulin | Fusion protein-pull down assay | Human | ARD domain | Not specified | Not determined | 20926660 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
