N-glycosylation alters cadherin-mediated intercellular binding kinetics

J Cell Sci. 2012 May 15;125(Pt 10):2478-85. doi: 10.1242/jcs.101147. Epub 2012 Feb 17.

Abstract

We present direct evidence that the N-glycosylation state of neural cadherin impacts the intrinsic kinetics of cadherin-mediated intercellular binding. Micropipette manipulation measurements quantified the effect of N-glycosylation mutations on intercellular binding dynamics. The wild-type protein exhibits a two-stage binding process in which a fast, initial binding step is followed by a short lag and second, slower transition to the final binding stage. Mutations that ablate N-glycosylation at three sites on the extracellular domains 2 and 3 of neural cadherin alter this kinetic fingerprint. Glycosylation does not affect the affinities between the adhesive N-terminal domains, but instead modulates additional cadherin interactions, which govern the dynamics of intercellular binding. These results, together with previous findings that these hypo-glycosylation mutations increase the prevalence of cis dimers on cell membranes, suggest a binding mechanism in which initial adhesion is followed by additional cadherin interactions, which enhance binding but are modulated by N-glycosylation. Given that oncogene expression drives specific changes in N-glycosylation, these results provide insight into possible mechanisms altering cadherin function during tumor progression.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • CHO Cells
  • Cadherins / chemistry*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cricetinae
  • Erythrocytes / metabolism
  • Glycosylation
  • Humans
  • Kinetics
  • Mice
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Cadherins