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Untangling desmosomal knots with electron tomography.

Wanzhong He1, Pamela Cowin, David L Stokes

  • 1Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA..

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Cell adhesion involves cadherin molecules in adherens junctions and desmosomes. This study visualizes cadherin tip interactions, revealing a flexible mechanism for cell adhesion and communication.

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Area of Science:

  • Cell biology
  • Structural biology
  • Biophysics

Background:

  • Cell adhesion is crucial for tissue integrity, mediated by cell junctions like adherens junctions and desmosomes.
  • Cadherin interactions are central to cell adhesion specificity and mechanics, but their precise molecular interfaces remain debated.

Purpose of the Study:

  • To visualize the in situ organization of cadherin molecules within desmosomes.
  • To elucidate the molecular mechanisms underlying cadherin-mediated cell adhesion specificity and dynamics.

Main Methods:

  • Utilized electron tomography on plastic-embedded neonatal mouse skin sections.
  • Generated high-resolution three-dimensional maps of desmosome structures.
  • Integrated C-cadherin crystal structure data with tomographic maps.

Main Results:

  • Revealed individual cadherin molecules organized in discrete clusters within desmosomes.
  • Demonstrated cadherin interactions occurring at their tips.
  • Identified a flexible intermolecular interface involving amino-terminal tryptophan exchange.

Conclusions:

  • Proposed a novel mechanism for cadherin cis and trans interactions mediated by flexible tip interactions.
  • Highlighted the role of this flexibility in propagating adhesive forces along cell junctions.
  • Provided new structural insights into the molecular basis of desmosome function.