J Am Soc Nephrol. 2008 Mar;19(3):469-76. doi: 10.1681/ASN.2006090985. Epub 2008 Jan 30.
Nek8 regulates the expression and localization of polycystin-1 and polycystin-2.
Sohara, E., Luo, Y., Zhang, J., Manning, D. K., Beier, D. R., Zhou, J.,
["Harvard Institutes of Medicine, Room 522, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA."]
["Harvard Institutes of Medicine, Room 522, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA."]
Nek8 is a serine/threonine kinase that is mutated in the jck (juvenile cystic kidneys) mouse, a model of autosomal recessive juvenile polycystic kidney disease, but its function is poorly understood. We used the jck mouse to study the functional relationship between Nek8 and other proteins that have been implicated in polycystic kidney diseases. In the collecting tubules and collecting ducts of wild-type mice, we found that Nek8 was localized to the proximal portion of primary cilia and was weakly detected in the cytosol. In the jck mutant, however, Nek8 was found along the entire length of cilia. Coimmunoprecipitation experiments demonstrated that Nek8 interacted with polycystin-2, but not with polycystin-1, and that the jck mutation did not affect this interaction. Western blot analysis and real-time reverse transcriptase PCR revealed that the protein and mRNA expression of polycystin-1 (PC1) and polycystin-2 (PC2) were increased in jck mouse kidneys. The jck mutation also led to abnormal phosphorylatin of PC2, and this was associated with longer cilia and ciliary accumulation of PC1 and PC2. Our data suggests that Nek8 interacts with the signal transduction pathways of the polycystins and may control the targeting of these ciliary proteins. Dysfunction Nek8 may lead to cystogenesis by altering the structure and function of cilia in the distal nephron.
PMID: 18235101
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
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NEK8 | Inference | Prediction | 18235101 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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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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NEK8 | Co-immunoprecipitation | Mouse kidney tissue | 18235101 | |||||
| TRPP1 |
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NEK8 | Co-immunoprecipitation | Mouse Inner medullary collecting duct cell | 18235101 | |||||
| TRPP1 |
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NEK8 | Co-immunofluorescence staining | Mouse kidney section | 18235101 | |||||
(:
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)