J Cell Biol. 2008 Aug 11;182(3):437-47. doi: 10.1083/jcb.200805124.
TRPP2 and TRPV4 form a polymodal sensory channel complex.
Kottgen, M., Buchholz, B., Garcia-Gonzalez, M. A., Kotsis, F., Fu, X., Doerken, M., Boehlke, C., Steffl, D., Tauber, R., Wegierski, T., Nitschke, R., Suzuki, M., Kramer-Zucker, A., Germino, G. G., Watnick, T., Prenen, J., Nilius, B., Kuehn, E. W., Walz, G.,
["Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."]
["Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany."]
The primary cilium has evolved as a multifunctional cellular compartment that decorates most vertebrate cells. Cilia sense mechanical stimuli in various organs, but the molecular mechanisms that convert the deflection of cilia into intracellular calcium transients have remained elusive. Polycystin-2 (TRPP2), an ion channel mutated in polycystic kidney disease, is required for cilia-mediated calcium transients but lacks mechanosensitive properties. We find here that TRPP2 utilizes TRPV4 to form a mechano- and thermosensitive molecular sensor in the cilium. Depletion of TRPV4 in renal epithelial cells abolishes flow-induced calcium transients, demonstrating that TRPV4, like TRPP2, is an essential component of the ciliary mechanosensor. Because TRPV4-deficient zebrafish and mice lack renal cysts, our findings challenge the concept that defective ciliary flow sensing constitutes the fundamental mechanism of cystogenesis.
PMID: 18695040

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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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TRPV4 | Inference | Prediction | 18695040 | |||||
TRPV4 |
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TRPP1 | Inference | Prediction | 18695040 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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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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TRPV4 | Co-immunoprecipitation | HEK293 | Human | C-terminus | Mouse | C-terminus | 18695040 | |
TRPP1 |
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TRPV4 | Co-immunofluorescence staining | MDCK | 18695040 | |||||
TRPP1 |
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TRPV4 | Fluorescence resonance energy transfer | HEK293 | Human | Full-length | Mouse | Full-length | 18695040 | |
TRPV4 |
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TRPP1 | Co-immunoprecipitation | HEK293 | Mouse | C-terminus | Human | C-terminus | 18695040 | |
TRPV4 |
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TRPP1 | Co-immunofluorescence staining | MDCK | 18695040 | |||||
TRPV4 |
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TRPP1 | Fluorescence resonance energy transfer | HEK293 | Mouse | Full-length | Human | Full-length | 18695040 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Functional consequence
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPP1 |
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TRPV4 | Patch clamp | New channel creation | 18695040 | |||||||
TRPV4 |
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TRPP1 | Patch clamp | New channel creation | 18695040 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
