Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells
Open Access
- 1 May 2009
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 122 (9), 1410-1417
- https://doi.org/10.1242/jcs.045021
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human renal disease and is caused by mutations in two genes, PKD1 (85%) and PKD2 (15%). Cyst epithelial cells are characterised by a complex cellular phenotype including changes in proliferation, apoptosis, basement membrane composition and apicobasal polarity. Since polycystin 1 (PC1), the PKD1 protein, has been located in the basolateral membrane of kidney epithelial cells, we hypothesised that it might have a key role in mediating or stabilising cell-cell interactions. In non-ciliated L929 cells, stable or transient surface expression of the PC1 extracellular domain was sufficient to confer an adhesive phenotype and stimulate junction formation. In MDCK cells, we found that PC1 was recruited to the lateral membranes coincident with E-cadherin within 30 minutes after a `calcium switch'. Recruitment of both proteins was significantly delayed when cells were treated with a PC1 blocking antibody raised to the PKD domains. Finally, PC1 and E-cadherin could be coimmunoprecipitated together from MDCK cells. We conclude that PC1 has a key role in initiating junction formation via initial homophilic interactions and facilitates junction assembly and the establishment of apicobasal polarity by E-cadherin recruitment.Keywords
This publication has 48 references indexed in Scilit:
- Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structureProceedings of the National Academy of Sciences of the United States of America, 2007
- Annexin A5 Interacts with Polycystin-1 and Interferes with the Polycystin-1 Stimulated Recruitment of E-cadherin into Adherens JunctionsJournal of Molecular Biology, 2007
- Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial CellsMolecular Biology of the Cell, 2007
- Mispolarization of desmosomal proteins and altered intercellular adhesion in autosomal dominant polycystic kidney diseaseAmerican Journal of Physiology-Renal Physiology, 2005
- Polycystic kidney disease: new understanding in the pathogenesisThe International Journal of Biochemistry & Cell Biology, 2004
- Sticky BusinessCell, 2003
- Polycystin-1 Interacts with Intermediate FilamentsPublished by Elsevier BV ,2001
- Polycystin-1 interacts with E-cadherin and the catenins—clues to the pathogenesis of cyst formation in ADPKD?Nephrology Dialysis Transplantation, 2000
- Cytomechanics of cadherin-mediated cell—cell adhesionCurrent Opinion in Cell Biology, 1998
- Expressed recombinant cadherins mediate cell sorting in model systemsCell, 1988