Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells

Andrew J. Streets, Bart E. Wagner, Peter C Harris, Christopher J. Ward, Albert C M Ong

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1410-1417
Number of pages8
JournalJournal of Cell Science
Volume122
Issue number9
DOIs
StatePublished - May 1 2009

Fingerprint

Madin Darby Canine Kidney Cells
Cadherins
Epithelial Cells
Phenotype
Kidney
Autosomal Dominant Polycystic Kidney
Blocking Antibodies
Membranes
polycystic kidney disease 1 protein
Basement Membrane
Cell Communication
Adhesives
Cysts
Apoptosis
Calcium
Mutation
Genes

Keywords

  • ADPKD
  • Cell adhesion
  • E-cadherin
  • MDCK
  • Polycystin 1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. / Streets, Andrew J.; Wagner, Bart E.; Harris, Peter C; Ward, Christopher J.; Ong, Albert C M.

In: Journal of Cell Science, Vol. 122, No. 9, 01.05.2009, p. 1410-1417.

Research output: Contribution to journalArticle

Streets, Andrew J. ; Wagner, Bart E. ; Harris, Peter C ; Ward, Christopher J. ; Ong, Albert C M. / Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. In: Journal of Cell Science. 2009 ; Vol. 122, No. 9. pp. 1410-1417.
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