Nature. 2005 Mar 3;434(7029):99-104.
Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain.
van Rossum, D. B., Patterson, R. L., Sharma, S., Barrow, R. K., Kornberg, M., Gill, D. L., Snyder, S. H.,
["Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
["Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
Many ion channels are regulated by lipids, but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels, components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-gamma1 that includes a partial pleckstrin homology (PH) domain-a consensus lipid-binding and protein-binding sequence. We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-gamma1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.
PMID: 15744307
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
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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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PLCƣ1 | Inference | Prediction | 15744307 | |||||
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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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| 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 | ||
| TRPC3 |
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PLCƣ1 | Yeast two-hybrid | Human | 1-171 | Yeast | Rat | 796-920 | Yeast | 15744307 |
| TRPV1 |
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PLCƣ1 | Yeast two-hybrid | Rat | 761-835 | Yeast | Rat | 796-920 | Yeast | 15744307 |
(:
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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| Characterization
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|---|---|---|---|---|---|---|---|---|---|---|
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPC3 |
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PLCƣ1 | Yeast two-hybrid | Human | 40-46 | Rat | 861-920 | 15744307 | ||
| TRPC3 |
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PLCƣ1 | Fusion protein-pull down assay | Human | 40-48 | Rat | 861-920 | 15744307 | ||
| TRPV1 |
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PLCƣ1 | Yeast two-hybrid | Rat | 761-835 | Rat | 861-920 | 15744307 | ||
(:
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
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPC3 |
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PLCƣ1 | Calcium measurement | Activation | 15744307 | |||||||
(:
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)