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Identification, Characterization, and Localization of a Novel Kidney Polycystin-1-Polycystin-2 Complex

Newby, L.J., Streets, A.J., Zhao, Y., Harris, P.C., Ward, C.J. and Ong, A.C.M. (2002) Identification, Characterization, and Localization of a Novel Kidney Polycystin-1-Polycystin-2 Complex. Journal of Biological Chemistry, 277 (73). 20763 - 20773. ISSN 1083-351X

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Abstract

The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a "polycystin complex" involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavily N-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and co-immunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Clinical Sciences Division North (Sheffield) > Sheffield Kidney Institute
Depositing User: Repository Officer
Date Deposited: 15 Aug 2005
Last Modified: 04 Jun 2014 14:40
Published Version: http://www.jbc.org/cgi/content/abstract/277/23/207...
Status: Published
Refereed: Yes
Identification Number: 10.1074/jbc.M107788200
URI: http://eprints.whiterose.ac.uk/id/eprint/586

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