Compromised cytoarchitecture and polarized trafficking in autosomal dominant polycystic kidney disease cells

Audra J. Charron, Sakie Nakamura, Robert Bacallao, Angela Wandinger-Ness

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Cystogenesis associated with autosomal dominant polycystic kidney disease (ADPKD) is characterized by perturbations in the polarized phenotype and function of cyst-lining epithelial cells. The polycystins, the protein products of the genes mutated in the majority of ADPKD cases, have been described recently, but the pathological mechanism by which causal mutations result in the mislocalization of cell membrane proteins has remained unclear. This report documents the dissociation from the ADPKD cell basolateral membrane of three molecules essential for spatial organization and exocytosis. The adherens junction protein E-cadherin, the subcellular disposition of which governs intercellular and intracellular architecture, was discovered sequestered in an internal ADPKD cell compartment. At the same time, sec6 and sec8, components of a complex critical for basolateral cargo delivery normally arrayed at the apico-lateral apex, were depleted from the ADPKD cell plasma membrane. An analysis of membrane transport revealed that basolateral trafficking of proteins and lipids was impaired as a result of delayed cargo exit from the ADPKD cell Golgi apparatus. Apical transport proceeded normally. Taken together with recent documentation of an association between polycystin-1 and E-cadherin (Huan and van Adelsberg, 1999), the data suggest that causal mutations disrupt E-cadherin-dependent cytoarchitecture, adversely affecting protein assemblies crucial for basolateral trafficking.

Original languageEnglish (US)
Pages (from-to)111-124
Number of pages14
JournalJournal of Cell Biology
Volume149
Issue number1
DOIs
StatePublished - Apr 3 2000

Keywords

  • Adherens junction
  • Autosomal dominant polycystic kidney disease (ADPKD)
  • Basolateral
  • Epithelia
  • Polycystin

ASJC Scopus subject areas

  • Cell Biology

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