Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion

Molly A. Thoreson, Panos Z. Anastasiadis, Juliet M. Daniel, Reneé C. Ireton, Margaret J. Wheelock, Keith R. Johnson, Diana K. Hummingbird, Albert B. Reynolds

Research output: Contribution to journalArticle

375 Scopus citations

Abstract

p120(ctn) is a catenin whose direct binding to the juxtamembrane domain of classical cadherins suggests a role in regulating cell-cell adhesion. The juxtamembrane domain has been implicated in a variety of roles including cadherin clustering, cell motility, and neuronal outgrowth, raising the possibility that p120 mediates these activities. We have generated minimal mutations in this region that uncouple the E-cadherin-p120 interaction, but do not affect interactions with other catenins. By stable transfection into E-cadherin-deficient cell lines, we show that cadherins are both necessary and sufficient for recruitment of p120 to junctions. Detergent-free subcellular fractionation studies indicated that, in contrast to previous reports, the stoichiometry of the interaction is extremely high. Unlike α- and β-catenins, p120 was metabolically stable in cadherin-deficient cells, and was present at high levels in the cytoplasm. Analysis of cells expressing E-cadherin mutant constructs indicated that p120 is required for the E- cadherin-mediated transition from weak to strong adhesion. In aggregation assays, cells expressing p120-uncoupled E-cadherin formed only weak cell aggregates, which immediately dispersed into single cells upon pipetting. As an apparent consequence, the actin cytoskeleton failed to insert properly into peripheral E-cadherin plaques, resulting in the inability to form a continuous circumferential ring around cell colonies. Our data suggest that p120 directly or indirectly regulates the E-cadherin-mediated transition to tight cell-cell adhesion, possibly blocking subsequent events necessary for reorganization of the actin cytoskeleton and compaction.

Original languageEnglish (US)
Pages (from-to)189-201
Number of pages13
JournalJournal of Cell Biology
Volume148
Issue number1
DOIs
StatePublished - Jan 10 2000

Keywords

  • Adherens junction
  • Catenin
  • Clustering
  • Compaction
  • Metastasis

ASJC Scopus subject areas

  • Cell Biology

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    Thoreson, M. A., Anastasiadis, P. Z., Daniel, J. M., Ireton, R. C., Wheelock, M. J., Johnson, K. R., Hummingbird, D. K., & Reynolds, A. B. (2000). Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. Journal of Cell Biology, 148(1), 189-201. https://doi.org/10.1083/jcb.148.1.189