Biochem Biophys Res Commun. 2007 Dec 28;364(4):861-6. doi: 10.1016/j.bbrc.2007.10.103. Epub 2007 Oct 26.
Kidney injury molecule 1 (Kim1) is a novel ciliary molecule and interactor of polycystin 2.
Kuehn, E. W., Hirt, M. N., John, A. K., Muehlenhardt, P., Boehlke, C., Putz, M., Kramer-Zucker, A. G., Bashkurov, M., van de Weyer, P. S., Kotsis, F., Walz, G.,
["Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany."]
["Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany."]
Inherited mutations in genes encoding for ciliary proteins lead to a broad spectrum of human diseases, such as polycystic kidney disease (PKD), situs inversus and retinitis pigmentosa. In the human kidney, autosomal dominant PKD (ADPKD) is caused by mutations in PKD1 (PC1), or PKD2 (TRPP2). Both are necessary for ciliary mechanotransduction, whereby bending of the cilium elicits a calcium response in the cell. We have previously shown that overexpression of mutated forms of the chemosensor kidney injury molecule 1 (Kim1) abolishes the flow response in ciliated MDCK cells. Here we identify Kim1 as an endogenous ciliary protein. Kim1 co-precipitates with TRPP2. Mutational analysis reveals that the interaction between Kim1 and TRPP2 requires the ciliary sorting motif in the N-terminus of TRPP2, and the presence of a highly conserved tyrosine in the intracellular tail of Kim1, which has previously been shown to play a role in ciliary flow sensing. These data support the notion that TRPP2 functionally interacts with ciliary chemosensors.
PMID: 18273441
 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 | |||
| TRPP1 |
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KIM1/TIM1 | Inference | Prediction | 18273441 | |||||
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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 | ||||
| TRPP1 |
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KIM1/TIM1 | Co-immunoprecipitation | HEK293T | Human | Full-length | Human | Full-length | 18273441 | |
(:
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
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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 | ||||
| TRPP1 |
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KIM1/TIM1 | Co-immunoprecipitation | Human | 1-30 | Human | Not determined | 18273441 | ||
(:
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)