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

373 Citations (Scopus)

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

Fingerprint

Cadherins
Catenins
Actin Cytoskeleton
Cell Adhesion
delta catenin
Cell Aggregation
Detergents
Cell Movement
Transfection
Cluster Analysis
Cytoplasm
Cell Line
Mutation

Keywords

  • Adherens junction
  • Catenin
  • Clustering
  • Compaction
  • Metastasis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Thoreson, M. A., Anastasiadis, P. Z., Daniel, J. M., Ireton, R. C., Wheelock, M. J., Johnson, K. R., ... 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

Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. / Thoreson, Molly A.; Anastasiadis, Panos Z.; Daniel, Juliet M.; Ireton, Reneé C.; Wheelock, Margaret J.; Johnson, Keith R.; Hummingbird, Diana K.; Reynolds, Albert B.

In: Journal of Cell Biology, Vol. 148, No. 1, 10.01.2000, p. 189-201.

Research output: Contribution to journalArticle

Thoreson, MA, Anastasiadis, PZ, Daniel, JM, Ireton, RC, Wheelock, MJ, Johnson, KR, Hummingbird, DK & Reynolds, AB 2000, 'Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion', Journal of Cell Biology, vol. 148, no. 1, pp. 189-201. https://doi.org/10.1083/jcb.148.1.189
Thoreson MA, Anastasiadis PZ, Daniel JM, Ireton RC, Wheelock MJ, Johnson KR et al. Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. Journal of Cell Biology. 2000 Jan 10;148(1):189-201. https://doi.org/10.1083/jcb.148.1.189
Thoreson, Molly A. ; Anastasiadis, Panos Z. ; Daniel, Juliet M. ; Ireton, Reneé C. ; Wheelock, Margaret J. ; Johnson, Keith R. ; Hummingbird, Diana K. ; Reynolds, Albert B. / Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. In: Journal of Cell Biology. 2000 ; Vol. 148, No. 1. pp. 189-201.
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