PLoS One. 2013;8(2):e58174. doi: 10.1371/journal.pone.0058174. Epub 2013 Feb 28.
A novel ion channel formed by interaction of TRPML3 with TRPV5.
Guo, Z., Grimm, C., Becker, L., Ricci, A. J., Heller, S.,
["Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America."]
["Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America."]
TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.
PMID: 23469151
 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 | |||
| TRPML3 |
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TRPV5 | Inference | Prediction | 23469151 | |||||
| TRPML3 |
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TRPV6 | Inference | Prediction | 23469151 | |||||
| TRPV5 |
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TRPML3 | Inference | Prediction | 23469151 | |||||
| TRPV6 |
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TRPML3 | Inference | Prediction | 23469151 | |||||
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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)
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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 | ||||
| TRPML1 |
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TRPML3 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPML2 |
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TRPML3 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPML3 |
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TRPML1 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPML3 |
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TRPML2 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPML3 |
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TRPV5 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Mouse | Full-length | 23469151 | |
| TRPML3 |
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TRPV6 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPV5 |
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TRPML3 | Fluorescence resonance energy transfer | HEK293 | Mouse | Full-length | Not specified | Full-length | 23469151 | |
| TRPV5 |
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TRPV6 | Fluorescence resonance energy transfer | HEK293 | Mouse | Full-length | Not specified | Full-length | 23469151 | |
| TRPV6 |
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TRPML3 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Not specified | Full-length | 23469151 | |
| TRPV6 |
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TRPV5 | Fluorescence resonance energy transfer | HEK293 | Not specified | Full-length | Mouse | Full-length | 23469151 | |
(:
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
|
| Characterization
|
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|---|---|---|---|---|---|---|---|---|---|---|
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPML3 |
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TRPV5 | Patch clamp | 1:1 | 23469151 | |||||
| TRPV5 |
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TRPML3 | Patch clamp | 1:1 | 23469151 | |||||
(:
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 | ||||||
| TRPML3 |
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TRPV5 | Patch clamp | New channel creation | 23469151 | |||||||
| TRPV5 |
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TRPML3 | Patch clamp | New channel creation | 23469151 | |||||||
(:
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)