J Cell Biol. 2008 Apr 7;181(1):143-55. doi: 10.1083/jcb.200712058. Epub 2008 Mar 31.
IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid.
Fernandes, J., Lorenzo, I. M., Andrade, Y. N., Garcia-Elias, A., Serra, S. A., Fernandez-Fernandez, J. M., Valverde, M. A.,
["Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain."]
["Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain."]
Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A(2) (PLA(2)) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA(2)-EET as the primary pathway to activate TRPV4. Under conditions of low PLA(2) activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)-inositol trisphosphate (IP(3)) signaling to support TRPV4 gating. IP(3), without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP(3) receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP(3) receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca(2+) channels required to initiate and maintain the oscillatory Ca(2+) signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA(2) activation.
PMID: 18378772
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
Screening
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPV4 |
|
IP3R3 | Inference | Prediction | 18378772 | |||||
(:
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
|
top
|
| Validation: In vivo validation
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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 | ||||
| TRPV4 |
|
IP3R3 | Co-immunoprecipitation | HeLa | Human | Full-length | Rat | Full-length | 18378772 | |
(:
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
|
top
|
| Functional consequence
|
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPV4 |
|
IP3R3 | Calcium measurement | Activation | 18378772 | |||||||
| TRPV4 |
|
IP3R3 | Patch clamp | Activation | 18378772 | |||||||
(:
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)