Mol Cell. 2002 Apr;9(4):739-50.
Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1.
Singh, B. B., Liu, X., Tang, J., Zhu, M. X., Ambudkar, I. S.,
["Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA."]
["Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA."]
The mechanism involved in [Ca(2+)](i)-dependent feedback inhibition of store-operated Ca(2+) entry (SOCE) is not yet known. Expression of Ca(2+)-insensitive calmodulin (Mut-CaM) but not wild-type CaM increased SOCE and decreased its Ca(2+)-dependent inactivation. Expression of TrpC1 lacking C terminus aa 664-793 (TrpC1DeltaC) also attenuated Ca(2+)-dependent inactivation of SOCE. CaM interacted with endogenous and expressed TrpC1 and with GST-TrpC1 C terminus but not with TrpC1DeltaC. Two CaM binding domains, aa 715-749 and aa 758-793, were identified. Expression of TrpC1Delta758-793 but not TrpC1Delta715-749 mimicked the effects of TrpC1DeltaC and Mut-CaM on SOCE. These data demonstrate that CaM mediates Ca(2+)-dependent feedback inhibition of SOCE via binding to a domain in the C terminus of TrpC1. These findings reveal an integral role for TrpC1 in the regulation of SOCE.
PMID: 11983166
 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 | |||
| TRPC1 |
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Calmodulin | Inference | Prediction | 11983166 | |||||
| TRPC1 |
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PMCA | Speculation | Prediction | 11983166 | |||||
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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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 | ||
| TRPC1 |
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Calmodulin | Fusion protein-pull down assay | Human | 649-793 | E. coli | Not specified | Full-length | Not specified | 11983166 |
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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 | ||||
| TRPC1 |
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PMCA | Co-immunoprecipitation | HSG cell | Human | Full-length | Not used | 11983166 | ||
(:
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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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 | ||||
| TRPC1 |
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Calmodulin | Fusion protein-pull down assay | Human | 719-751 | Not specified | Not determined | 11983166 | ||
| TRPC1 |
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Calmodulin | Fusion protein-pull down assay | Human | 758-793 | Not specified | Not determined | 11983166 | ||
(:
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:
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|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPC1 |
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Calmodulin | Patch clamp | Inhibition | 11983166 | |||||||
| TRPC1 |
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Calmodulin | Calcium measurement | Inhibition | 11983166 | |||||||
(:
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