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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
N-glycosylation alters cadherin-mediated intercellular binding kinetics
Matthew D Langer1, Huabei Guo, Nitesh Shashikanth
1Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Journal of Cell Science
|February 21, 2012
Summary
Neural cadherin
Area of Science:
- Cell adhesion
- Glycobiology
- Biophysics
Background:
- Neural cadherin (N-cadherin) mediates cell-cell adhesion.
- N-cadherin's function is crucial in development and disease, including cancer progression.
- The role of N-cadherin's post-translational modifications, like N-glycosylation, in its binding kinetics remains unclear.
Purpose of the Study:
- To investigate the direct impact of N-cadherin N-glycosylation state on the kinetics of intercellular binding.
- To elucidate how N-glycosylation modulates N-cadherin-mediated adhesion dynamics.
Main Methods:
- Micropipette manipulation experiments were employed to quantify intercellular binding dynamics.
- Site-directed mutagenesis was used to ablate N-glycosylation at specific sites on N-cadherin's extracellular domains.
Main Results:
- Wild-type N-cadherin exhibits a two-stage binding process with distinct kinetic phases.
- Mutations disrupting N-glycosylation altered the binding kinetics, affecting the transition between binding stages.
- N-glycosylation does not influence the affinity of N-terminal domains but modulates other cadherin interactions.
Conclusions:
- N-glycosylation is a key regulator of N-cadherin-mediated intercellular binding dynamics, independent of direct N-terminal domain affinity.
- Altered N-glycosylation, potentially driven by oncogenes, may contribute to aberrant cadherin function in tumor progression.
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