| First Author | Newby LJ | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 23 | Pages | 20763-73 |
| PubMed ID | 11901144 | Mgi Jnum | J:77086 |
| Mgi Id | MGI:2180983 | Doi | 10.1074/jbc.M107788200 |
| Citation | Newby LJ, et al. (2002) Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J Biol Chem 277(23):20763-73 |
| abstractText | 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. |
