Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3934-9.
Specific association of the gene product of PKD2 with the TRPC1 channel.
Tsiokas, L., Arnould, T., Zhu, C., Kim, E., Walz, G., Sukhatme, V. P.,
["Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA."]
["Renal Division, RW 563, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA."]
The function(s) of the genes (PKD1 and PKD2) responsible for the majority of cases of autosomal dominant polycystic kidney disease is unknown. While PKD1 encodes a large integral membrane protein containing several structural motifs found in known proteins involved in cell-cell or cell-matrix interactions, PKD2 has homology to PKD1 and the major subunit of the voltage-activated Ca2+ channels. We now describe sequence homology between PKD2 and various members of the mammalian transient receptor potential channel (TRPC) proteins, thought to be activated by G protein-coupled receptor activation and/or depletion of internal Ca2+ stores. We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and in vitro. This association is mediated by two distinct domains in PKD2. One domain involves a minimal region of 73 amino acids in the C-terminal cytoplasmic tail of PKD2 shown previously to constitute an interacting domain with PKD1. However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1. The C-terminal domain is sufficient but not necessary for the PKD2-TRPC1 association. A more N-terminal domain located within transmembrane segments S2 and S5, including a putative pore helical region between S5 and S6, is also responsible for the association. Given the ability of the TRPC to form functional homo- and heteromultimeric complexes, these data provide evidence that PKD2 may be functionally related to TRPC proteins and suggest a possible role of PKD2 in modulating Ca2+ entry in response to G protein-coupled receptor activation and/or store depletion.
PMID: 10097141

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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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TRPP1 | Inference | Prediction | 10097141 | |||||
TRPP1 |
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TRPC1 | Inference | Prediction | 10097141 |
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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 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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TRPP1 | Fusion protein-pull down assay | Human | 662-750 | E. coli | Human | 680-968 | In vitro translation | 10097141 |
TRPP1 |
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TRPC1 | Fusion protein-pull down assay | Human | 680-968 | In vitro translation | Human | 662-750 | E. coli | 10097141 |
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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 | ||||
TRPC1 |
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TRPP1 | Co-immunoprecipitation | HEK293T | Human | Full-length | Human | Full-length | 10097141 | |
TRPC1 |
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TRPP1 | Co-immunofluorescence staining | HEK293T | Human | Full-length | Human | Full-length | 10097141 | |
TRPP1 |
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TRPC1 | Co-immunoprecipitation | HEK293T | Human | Full-length | Human | Full-length | 10097141 | |
TRPP1 |
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TRPC1 | Co-immunofluorescence staining | HEK293T | Human | Full-length | Human | Full-length | 10097141 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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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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TRPP1 | Co-immunoprecipitation | Human | Not determined | Human | 1-643 | 10097141 | ||
TRPC1 |
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TRPP1 | Co-immunoprecipitation | Human | Not determined | Human | 679-968 | 10097141 | ||
TRPC1 |
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TRPP1 | Yeast two-hybrid | Human | 639-750 | Human | 822-895 | 10097141 | ||
TRPP1 |
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PKD1/Polycystin-1 | Yeast two-hybrid | Human | 822-895 | Human | 4124-4303 | 10097141 | ||
TRPP1 |
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TRPC1 | Co-immunoprecipitation | Human | 1-643 | Human | Not determined | 10097141 | ||
TRPP1 |
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TRPC1 | Co-immunoprecipitation | Human | 679-968 | Human | Not determined | 10097141 | ||
TRPP1 |
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TRPC1 | Yeast two-hybrid | Human | 822-895 | Human | 639-750 | 10097141 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
