Nature. 2000 Dec 21-28;408(6815):990-4.
Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
Hanaoka, K., Qian, F., Boletta, A., Bhunia, A. K., Piontek, K., Tsiokas, L., Sukhatme, V. P., Guggino, W. B., Germino, G. G.,
["Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
["Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA."]
The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals. Mutations in either PKD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell-cell or cell-matrix interactions, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin-1 nor -2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either polycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.
PMID: 11140688

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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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PKD1/Polycystin-1 | Co-immunofluorescence staining | CHO | Human | Full-length | Human | Full-length | 11140688 | |
TRPP1 |
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PKD1/Polycystin-1 | Co-immunoprecipitation | CHO | Human | Full-length | Human | Full-length | 11140688 |
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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 | ||||
TRPP1 |
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PKD1/Polycystin-1 | Co-immunoprecipitation | Human | 742-968 | Human | 4227-4303 | 11140688 |
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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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PKD1/Polycystin-1 | Co-immunofluorescence staining | Increase in plasma membrane level | 11140688 | |||||||
TRPP1 |
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PKD1/Polycystin-1 | Patch clamp | New channel creation | 11140688 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
