A Polycystin-1 Multiprotein Complex is Disrupted in Polycystic Kidney Disease Cells

Tamara Roitbak, Christopher J. Ward, Peter C Harris, Robert Bacallao, Scott A. Ness, Angela Wandinger-Ness

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is typified by the accumulation of fluid-filled cysts and abnormalities in renal epithelial cell function. The disease is principally caused by mutations in the gene encoding polycystin-1, a large basolateral plasma membrane protein expressed in kidney epithelial cells. Our studies reveal that, in normal kidney cells, polycystin-1 forms a complex with the adherens junction protein E-cadherin and its associated catenins, suggesting a role in cell adhesion or polarity. In primary cells from ADPKD patients, the polycystin-1/ polycystin-2/E-cadherin/β -catenin complex was disrupted and both polycystin-1 and E-cadherin were depleted from the plasma membrane as a result of the increased phosphorylation of polycystin-1. The loss of E-cadherin was compensated by the transcriptional upregulation of the normally mesenchymal N-cadherin. Increased cell surface N-cadherin in the disease cells in turn stabilized the continued plasma membrane localization of β-catenin in the absence of E-cadherin. The results suggest that enhanced phosphorylation of polycystin-1 in ADPKD cells precipitates changes in its localization and its ability to form protein complexes that are critical for the stabilization of adherens junctions and the maintenance of a fully differentiated polarized renal epithelium.

Original languageEnglish (US)
Pages (from-to)1334-1346
Number of pages13
JournalMolecular Biology of the Cell
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2004

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Multiprotein Complexes
Polycystic Kidney Diseases
Cadherins
Autosomal Dominant Polycystic Kidney
Catenins
Kidney
Adherens Junctions
Cell Membrane
Epithelial Cells
Phosphorylation
Cyst Fluid
Cell Polarity
polycystic kidney disease 1 protein
Cell Adhesion
Blood Proteins
Membrane Proteins
Proteins
Up-Regulation
Epithelium
Maintenance

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

A Polycystin-1 Multiprotein Complex is Disrupted in Polycystic Kidney Disease Cells. / Roitbak, Tamara; Ward, Christopher J.; Harris, Peter C; Bacallao, Robert; Ness, Scott A.; Wandinger-Ness, Angela.

In: Molecular Biology of the Cell, Vol. 15, No. 3, 01.03.2004, p. 1334-1346.

Research output: Contribution to journalArticle

Roitbak, Tamara ; Ward, Christopher J. ; Harris, Peter C ; Bacallao, Robert ; Ness, Scott A. ; Wandinger-Ness, Angela. / A Polycystin-1 Multiprotein Complex is Disrupted in Polycystic Kidney Disease Cells. In: Molecular Biology of the Cell. 2004 ; Vol. 15, No. 3. pp. 1334-1346.
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