Unknown

Dataset Information

0

A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease cells.


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/beta-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 beta-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.

SUBMITTER: Roitbak T 

PROVIDER: S-EPMC363138 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease cells.

Roitbak Tamara T   Ward Christopher J CJ   Harris Peter C PC   Bacallao Robert R   Ness Scott A SA   Wandinger-Ness Angela A  

Molecular biology of the cell 20040112 3


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 ce  ...[more]

Similar Datasets

| S-EPMC1317661 | biostudies-literature
| S-EPMC3484456 | biostudies-literature
| S-EPMC3785271 | biostudies-literature
| S-EPMC6731238 | biostudies-literature
| S-EPMC2781709 | biostudies-literature
| S-EPMC9342640 | biostudies-literature
| S-EPMC4378096 | biostudies-literature
| S-EPMC8729842 | biostudies-literature
| S-EPMC1459378 | biostudies-literature
| S-EPMC2834200 | biostudies-literature