N-glycosylation alters cadherin-mediated intercellular binding kinetics

Matthew D. Langer, Huabei Guo, Nitesh Shashikanth, J. Michael Pierce, Deborah E Leckband

Research output: Contribution to journalArticle

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 Nterminal 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.

Original languageEnglish (US)
Pages (from-to)2478-2485
Number of pages8
JournalJournal of cell science
Volume125
Issue number10
DOIs
StatePublished - Aug 14 2012

Fingerprint

Cadherins
Glycosylation
Mutation
Dermatoglyphics
Oncogenes
Adhesives
Cell Membrane
Neoplasms
Proteins

Keywords

  • Cadherins
  • Cell adhesion
  • Glycosylation
  • Kinetics
  • Micropipette

ASJC Scopus subject areas

  • Cell Biology

Cite this

N-glycosylation alters cadherin-mediated intercellular binding kinetics. / Langer, Matthew D.; Guo, Huabei; Shashikanth, Nitesh; Pierce, J. Michael; Leckband, Deborah E.

In: Journal of cell science, Vol. 125, No. 10, 14.08.2012, p. 2478-2485.

Research output: Contribution to journalArticle

Langer, Matthew D. ; Guo, Huabei ; Shashikanth, Nitesh ; Pierce, J. Michael ; Leckband, Deborah E. / N-glycosylation alters cadherin-mediated intercellular binding kinetics. In: Journal of cell science. 2012 ; Vol. 125, No. 10. pp. 2478-2485.
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