Mechanism of extracellular domain-deleted dominant negative cadherins

Marvin T. Nieman, Jae Beom Kim, Keith R. Johnson, Margaret J. Wheelock

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

The cadherin/catenin complex mediates Ca2+-dependent cell-cell interactions that are essential for normal developmental processes. It has been proposed that sorting of cells during embryonic development is due, at least in part, to expression of different cadherin family members or to expression of differing levels of a single family member. Expression of dominant-negative cadherins has been used experimentally to decrease cell-cell interactions in whole organisms and in cultured cells. In this study, we elucidated the mechanism of action of extracellular domain-deleted dominant-negative cadherin, showing that it is not cadherin isotype-specific, and that it must be membrane-associated but the orientation within the membrane does not matter. In addition, membrane-targeted cytoplasmic domain cadherin with tile catenin-binding domain deleted does not function as a dominant-negative cadherin. Expression of extracellular domain-deleted dominant-negative cadherin results in down-regulation of endogenous cadherins which presumably contributes to the non-adhesive phenotype.

Original languageEnglish (US)
Pages (from-to)1621-1632
Number of pages12
JournalJournal of cell science
Volume112
Issue number10
StatePublished - 1999

Keywords

  • Adherens junction
  • Catenin
  • Cell adhesion
  • E-cadherin
  • N-cadherin

ASJC Scopus subject areas

  • Cell Biology

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