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
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.
|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|