Intercellular adhesion mediated by human muscle neural cell adhesion molecule: effects of alternative exon use

J A Pizzey1, L H Rowett, C H Barton

  • 1Department of Neurochemistry, Institute of Neurology, Queen Square, London, United Kingdom.

Insights

Neural cell adhesion molecule (N-CAM) isoforms, when transfected into mouse fibroblasts, significantly increased cell adhesion. Specific N-CAM forms mediated homophilic binding, while heparin inhibited adhesion.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Neural cell adhesion molecule (N-CAM) plays a crucial role in cell-cell interactions.
  • Different N-CAM isoforms exist, including transmembrane, GPI-linked, and secreted forms, with varying functional implications.
  • Understanding the specific adhesive properties of each N-CAM isoform is essential for comprehending cell behavior.

Purpose of the Study:

  • To investigate the adhesive properties of different neural cell adhesion molecule (N-CAM) isoforms.
  • To determine the role of transmembrane, GPI-linked, and secreted N-CAM in intercellular adhesion.
  • To analyze the specificity of N-CAM-mediated cell aggregation.

Main Methods:

  • Permanent transfection of mouse 3T3 fibroblasts with cDNAs encoding human skeletal muscle and brain N-CAM isoforms.
  • Adhesion assays conducted under varying conditions, including the absence of external shear forces.
  • Coaggregation assays using fluorescently labeled and unlabeled cell populations to measure aggregation specificity.

Main Results:

  • Transfection with transmembrane or GPI-linked N-CAM significantly increased 3T3 cell adhesion in suspension.
  • Secreted N-CAM isoform transfection had no effect on cell adhesion.
  • Heparin inhibited N-CAM-mediated adhesion, with higher concentrations affecting parental cell adhesion.
  • Evidence of homophilic binding was observed between cells expressing surface-bound N-CAM isoforms.

Conclusions:

  • Surface-bound N-CAM isoforms (transmembrane and GPI-linked) mediate intercellular adhesion.
  • The secreted N-CAM isoform does not contribute to cell adhesion in this context.
  • N-CAM-mediated adhesion exhibits specificity, indicating homophilic interactions.
  • Heparin acts as an inhibitor of N-CAM-mediated cell adhesion.

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