Calcium-dependent dynamics of cadherin interactions at cell-cell junctions

Sally A. Kim, Chin Yin Tai, Lee Peng Mok, Eric A. Mosser, Erin M. Schuman

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Cadherins play a key role in the dynamics of cell-cell contact formation and remodeling of junctions and tissues. Cadherin-cadherin interactions are gated by extracellular Ca2+, which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 ± 0.06 s-1) upon chelation of extracellular Ca2+. A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 ± 0.02 s-1), suggesting two types of native cadherin interactions - one that is rapidly modulated by changes in extracellular Ca2+ and another with relatively stable adhesive activity that is Ca2+ independent. The Ca2+-sensitive dynamics of cadherin interactions were transmitted to the cell interior where β-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.

Original languageEnglish (US)
Pages (from-to)9857-9862
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number24
DOIs
StatePublished - Jun 14 2011

Keywords

  • Cell adhesion
  • Fluorescence resonance energy transfer
  • Trans binding

ASJC Scopus subject areas

  • General

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