Circ Res. 2005 Nov 25;97(11):1164-72. Epub 2005 Oct 27.
Activation of the endothelial store-operated ISOC Ca2+ channel requires interaction of protein 4.1 with TRPC4.
Cioffi, D. L., Wu, S., Alexeyev, M., Goodman, S. R., Zhu, M. X., Stevens, T.,
["Center for Lung Biology, Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL 36688, USA."]
["Center for Lung Biology, Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL 36688, USA."]
Store-operated calcium (SOC) entry represents the principal Ca2+ entry pathway into nonexcitable cells. Despite intensive investigation, mechanisms underlying activation of SOC entry have remained elusive. The endothelial ISOC channel is a Ca2+-selective SOC entry channel to which the transient receptor potential (TRP) proteins TRPC1 and TRPC4 contribute subunits. Activation of ISOC is specifically regulated by the spectrin-actin membrane skeleton; however, the nature of coupling between the ISOC channel and membrane skeleton is unknown. Here we demonstrate that protein 4.1 is an essential component of the ISOC channel gating mechanism. Protein 4.1 interacts with TRPC4 and the membrane skeleton. Deletion of the protein 4.1 binding domain on TRPC4 or peptide competition to the protein 4.1 binding domain prevents ISOC activation. These findings reveal that interaction of protein 4.1 with TRPC4 is required for activation of the endothelial ISOC channel.
PMID: 16254212
 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 | |||
| TRPC4 |
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Protein 4.1 | Inference | Prediction | 16254212 | |||||
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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 | ||||
| TRPC4 |
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Protein 4.1 | Co-immunoprecipitation | Rat pumonary aortic endothelial cell | 16254212 | |||||
(:
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
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| Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPC4 |
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Protein 4.1 | Calcium measurement | Activation | 16254212 | |||||||
| TRPC4 |
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Protein 4.1 | Patch clamp | Activation | 16254212 | |||||||
(:
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)