Cadherin function in junctional complex rearrangement and posttranslational control of cadherin expression
| Autor: | Nicole Cobb, James A. Marrs, Yih Tai Chen, Megan L. Troxell, W. James Nelson |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Tight junction
Physiology Cadherin Recombinant Fusion Proteins Cell Biology Biology Cadherins Fusion protein Cell junction Adhesion protein Cell Line Cell biology Adherens junction Dogs Intercellular Junctions Cell culture Mutation Animals Amino Acid Sequence Protein Processing Post-Translational Function (biology) Glycoproteins |
| Zdroj: | American Journal of Physiology-Cell Physiology. 276:C404-C418 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1999.276.2.c404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|