α-Catenin mediates initial E-cadherin-dependent cell- cell recognition and subsequent bond strengthening

Saumendra Bajpai, Joana Correia, Yunfeng Feng, Joana Figueiredo, Sean X. Sun, Gregory D. Longmore, Gianpaolo Suriano, Denis Wirtz

Research output: Contribution to journalArticle

Abstract

α-Catenin is essential in cadherin-mediated epithelium development and maintenance of tissues and in cancer progression and metastasis. However, recent studies question the conventional wisdom that α-catenin directly bridges the cadherin adhesion complex to the actin cytoskeleton. Therefore, whether α-catenin plays a direct role in cadherin-dependent cell adhesion is unknown. Here, single-molecule force spectroscopy measurements in cells depleted of α-catenin or expressing the hereditary diffuse gastric cancer associated V832M E-cadherin germ-line missense mutation show that α-catenin plays a critical role in cadherin-mediated intercellular recognition and subsequent multibond formation within the first 300 ms of cell contact. At short contact times, α-catenin mediates a 30% stronger interaction between apposing E-cadherin molecules than when it cannot bind the E-cadherin-β-catenin complex. As contact time between cells increases, α-catenin is essential for the strengthening of the first intercellular cadherin bond and for the ensuing formation of additional bonds between the cells, all without the intervention of actin. These results suggest that a critical decision to form an adhesion complex between 2 cells occurs within an extremely short time span and at a single-molecule level and identify a previously unappreciated role for α-catenin in these processes.

Original languageEnglish (US)
Pages (from-to)18331-18336
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
StatePublished - Nov 25 2008

Keywords

  • Actin
  • Cancer
  • Cell adhesion
  • Single-molecule force spectroscopy

ASJC Scopus subject areas

  • General

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