Modulating the strength of cadherin adhesion

Evidence for a novel adhesion complex

Young J. Kim, Christa Sauer, Karla Testa, James K Wahl, Robert A. Svoboda, Keith R Johnson, Margaret J. Wheelock, Karen A. Knudsen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Adherens junctions and desmosomes are critical for embryogenesis and the integrity of adult tissues. To form these junctions, classical cadherins interact via α- and β-catenin with the actin cytoskeleton, whereas desmosomal cadherins interact with the intermediate filament system. Here, we used a hormone-activated mutant N-cadherin expressed in fibroblasts to show the existence of a novel classical cadherin adhesion system. N-cadherin was fused at its C-terminus to a modified estrogen receptor ligand-binding domain (NcadER) that binds 4-hydroxytamoxifen (4OHT) and expressed in L cells, which lack an endogenous cadherin. Cells with the mutant cadherin (LNER cells) aggregated in the absence of 4OHT, but only in its presence formed tightly compacted aggregates like those formed by L cells expressing wild-type N-cadherin (LN cells). Compaction of LNER cells treated with 4OHT was accompanied by elevated levels of p120ctn in NcadER immunoprecipitates, compared to immunoprecipitates of non-treated cells, but without changes in α- and β-catenin, or actin. Compaction induced by 4OHT was also accompanied by increased interaction of the NcadER with the cytoskeleton and increased vimentin organization. Vimentin co-immunoprecipitated with the NcadER/catenin complex, suggesting an interaction between cadherin and vimentin. The mechanism by which vimentin interacts with the cadherin appears to involve p120ctn as it co-immunoprecipitates and colocalizes with vimentin in the parent L cells, which lack a cadherin and α- and β-catenins. Disrupting the actin cytoskeleton with cytochalasin B inhibited aggregation, whereas knocking down vimentin with specific siRNAs inhibited compaction. Based on our results we propose that a vimentin-based classical cadherin complex functions together with the actin-based complex to promote strong cell-cell adhesion in fibroblasts.

Original languageEnglish (US)
Pages (from-to)3883-3894
Number of pages12
JournalJournal of Cell Science
Volume118
Issue number17
DOIs
StatePublished - Sep 1 2005

Fingerprint

Cadherins
Vimentin
Catenins
Actin Cytoskeleton
Actins
Desmosomal Cadherins
Fibroblasts
Adherens Junctions
Desmosomes
Cytochalasin B
Intermediate Filaments
Cytoskeleton
Cell Adhesion
Estrogen Receptors
Embryonic Development
Hormones
Ligands

Keywords

  • Actin
  • Cadherin
  • Catenins
  • Cell-cell adhesion
  • Junctions
  • Vimentin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Modulating the strength of cadherin adhesion : Evidence for a novel adhesion complex. / Kim, Young J.; Sauer, Christa; Testa, Karla; Wahl, James K; Svoboda, Robert A.; Johnson, Keith R; Wheelock, Margaret J.; Knudsen, Karen A.

In: Journal of Cell Science, Vol. 118, No. 17, 01.09.2005, p. 3883-3894.

Research output: Contribution to journalArticle

Kim, YJ, Sauer, C, Testa, K, Wahl, JK, Svoboda, RA, Johnson, KR, Wheelock, MJ & Knudsen, KA 2005, 'Modulating the strength of cadherin adhesion: Evidence for a novel adhesion complex', Journal of Cell Science, vol. 118, no. 17, pp. 3883-3894. https://doi.org/10.1242/jcs.02508
Kim, Young J. ; Sauer, Christa ; Testa, Karla ; Wahl, James K ; Svoboda, Robert A. ; Johnson, Keith R ; Wheelock, Margaret J. ; Knudsen, Karen A. / Modulating the strength of cadherin adhesion : Evidence for a novel adhesion complex. In: Journal of Cell Science. 2005 ; Vol. 118, No. 17. pp. 3883-3894.
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