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J. Cell Biol.,
Volume 144, Number 4, February 22, 1999 687-699
-Catenin Complex to
Efficient Endoplasmic Reticulum Exit and Basal-lateral
Membrane Targeting of E-Cadherin in Polarized MDCK Cells
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5435
The E-cadherin/catenin complex regulates
Ca++-dependent cell-cell adhesion and is localized to
the basal-lateral membrane of polarized epithelial cells.
Little is known about mechanisms of complex assembly
or intracellular trafficking, or how these processes might ultimately regulate adhesion functions of the
complex at the cell surface. The cytoplasmic domain of
E-cadherin contains two putative basal-lateral sorting
motifs, which are homologous to sorting signals in the
low density lipoprotein receptor, but an alanine scan
across tyrosine residues in these motifs did not affect
the fidelity of newly synthesized E-cadherin delivery to the basal-lateral membrane of MDCK cells. Nevertheless, sorting signals are located in the cytoplasmic domain since a chimeric protein (GP2CAD1), comprising
the extracellular domain of GP2 (an apical membrane
protein) and the transmembrane and cytoplasmic domains of E-cadherin, was efficiently and specifically delivered to the basal-lateral membrane. Systematic deletion and recombination of specific regions of the
cytoplasmic domain of GP2CAD1 resulted in delivery
of <10% of these newly synthesized proteins to both apical and basal-lateral membrane domains. Significantly, >90% of each mutant protein was retained in
the ER. None of these mutants formed a strong interaction with 
-catenin, which normally occurs shortly after
E-cadherin synthesis. In addition, a simple deletion mutation of E-cadherin that lacks -catenin binding is also
localized intracellularly. Thus, -catenin binding to the
whole cytoplasmic domain of E-cadherin correlates
with efficient and targeted delivery of E-cadherin to the
lateral plasma membrane. In this capacity, we suggest
that -catenin acts as a chauffeur, to facilitate transport of E-cadherin out of the ER and the plasma membrane.
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