Cadherin function in junctional complex rearrangement and posttranslational control of cadherin expression

Megan L. Troxell, Yih Tai Chen, Nicole Cobb, W. James Nelson, James A. Marrs

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The role of E-cadherin, a calcium-dependent adhesion protein, in organizing and maintaining epithelial junctions was examined in detail by expressing a fusion protein (GP2-Cad1) composed of the extracellular domain of a nonadherent glycoprotein (GP2) and the transmembrane and cytoplasmic domains of E-cadherin. All studies shown were also replicated using an analogous cell line that expresses a mutant cadherin construct (T151) under the control of tet repressor. Mutant cadherin was expressed at ~10% of the endogenous E-cadherin level and had no apparent effect on tight junction function or on distributions of adherens junction, tight junction, or desmosomal marker proteins in established Madin-Darby canine kidney cell monolayers. However, GP2-Cad1 accelerated the disassembly of epithelial junctional complexes and delayed their reassembly in calcium switch experiments. Inducing expression of GP2-Cad1 to levels approximately threefold greater than endogenous E-cadherin expression levels in control cells resulted in a decrease in endogenous E-cadherin levels. This was due in part to increased protein turnover, indicating a cellular mechanism for sensing and controlling E-cadherin levels. Cadherin association with catenins is necessary for strong cadherin-mediated cell-cell adhesion. In cells expressing low levels of GP2-Cad1, protein levels and stoichiometry of the endogenous cadherin-catenin complex were unaffected. Thus effects of GP2- Cad1 on epithelial junctional complex assembly and stability were not due to competition with endogenous E-cadherin for catenin binding. Rather, we suggest that GP2-Cad1 interferes with the packing of endogenous cadherin- catenin complexes into higher-order structures in junctional complexes that results in junction destabilization.

Original languageEnglish (US)
Pages (from-to)C404-C418
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number2 45-2
StatePublished - Mar 5 1999

Keywords

  • Adherens junction
  • E-cadherin
  • Tight junction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    Troxell, M. L., Chen, Y. T., Cobb, N., Nelson, W. J., & Marrs, J. A. (1999). Cadherin function in junctional complex rearrangement and posttranslational control of cadherin expression. American Journal of Physiology - Cell Physiology, 276(2 45-2), C404-C418.