Pain. 2008 Sep 15;138(3):604-16. doi: 10.1016/j.pain.2008.02.022. Epub 2008 Apr 1.
A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1.
Jeske, N. A., Diogenes, A., Ruparel, N. B., Fehrenbacher, J. C., Henry, M., Akopian, A. N., Hargreaves, K. M.,
["Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center of San Antonio, MC 7908, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. jeske@UTHSCSA.edu"]
["Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center of San Antonio, MC 7908, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. jeske@UTHSCSA.edu"]
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.
PMID: 18381233
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPV1 |
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AKAP5/AKAP150 | Inference | Prediction | 18381233 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Validation: In vivo validation
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| 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 | ||||
| TRPV1 |
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AKAP5/AKAP150 | Co-immunofluorescence staining | Rat trigeminal ganglia neuron | 18381233 | |||||
| TRPV1 |
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AKAP5/AKAP150 | Co-immunoprecipitation | Rat trigeminal ganglia neuron | 18381233 | |||||
| TRPV1 |
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AKAP5/AKAP150 | Co-immunoprecipitation | CHO | Rat | Full-length | Rat | Full-length | 18381233 | |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPV1 |
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AKAP5/AKAP150 | In vivo PTM assay | Phosphorylation | 18381233 | |||||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)