A Dileucine Motif Targets E-cadherin to the Basolateral Cell Surface in Madin-Darby Canine Kidney and LLC-PK1 Epithelial Cells

Kevin C. Miranda, Tatiana Khromykh, Perpetina Christy, Tam Luan Le, Cara J. Gottardi, Alpha S. Yap, Jennifer L. Stow, Rohan D. Teasdale*

*Corresponding author for this work

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

E-cadherin is a major adherens junction protein of epithelial cells, with a central role in cell-cell adhesion and cell polarity. Newly synthesized E-cadherin is targeted to the basolateral cell surface. We analyzed targeting information in the cytoplasmic tail of E-cadherin by utilizing chimeras of E-cadherin fused to the ectodomain of the interleukin-2α (IL-2α) receptor expressed in Madin-Darby canine kidney and LLC-PK1 epithelial cells. Chimeras containing the full-length or membrane-proximal half of the E-cadherin cytoplasmic tail were correctly targeted to the basolateral domain. Sequence analysis of the membrane-proximal tail region revealed the presence of a highly conserved dileucine motif, which was analyzed as a putative targeting signal by mutagenesis. Elimination of this motif resulted in the loss of Tac/E-cadherin basolateral localization, pin-pointing this dileucine signal as being both necessary and sufficient for basolateral targeting of E-cadherin. Truncation mutants unable to bind β-catenin were correctly targeted, showing, contrary to current understanding, that β-catenin is not required for basolateral trafficking. Our results also provide evidence that dileucine-mediated targeting is maintained in LLC-PK 1 cells despite the altered polarity of basolateral proteins with tyrosine-based signals in this cell line. These results provide the first direct insights into how E-cadherin is targeted to the basolateral membrane.

Original languageEnglish (US)
Pages (from-to)22565-22572
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
StatePublished - Jun 22 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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