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

Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9857-62. doi: 10.1073/pnas.1019003108. Epub 2011 May 25.

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 Ca(2+), 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 Ca(2+). 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 Ca(2+) and another with relatively stable adhesive activity that is Ca(2+) independent. The Ca(2+)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Chlorocebus aethiops
  • Fluorescence Resonance Energy Transfer
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Intercellular Junctions / metabolism*
  • Kinetics
  • L Cells
  • Mice
  • Microscopy, Confocal
  • Protein Binding / drug effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Cadherins
  • Recombinant Fusion Proteins
  • beta Catenin
  • Green Fluorescent Proteins
  • Calcium