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Adhesive interactions between alternatively spliced CD44 isoforms

A Droll1, S T Dougherty, R K Chiu

  • 1Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Agency, Vancouver, Canada.

The Journal of Biological Chemistry
|May 12, 1995
PubMed
Summary
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CD44 isoforms CD44H and CD44R1 bind hyaluronan, but only CD44R1 promotes cell aggregation. CD44R1 recognizes a determinant distinct from the hyaluronan-binding site, influencing cell adhesion.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Alternative splicing of the CD44 gene generates numerous isoforms with varying functions.
  • The impact of specific inserted domains on CD44 ligand-binding specificity is not well understood.

Purpose of the Study:

  • To investigate the functional differences between CD44 isoforms, specifically CD44H and CD44R1.
  • To determine the effect of CD44 isoforms on cellular aggregation and ligand binding.

Main Methods:

  • Transduction of CD44-negative murine lymphoma cells (TIL1) with different CD44 isoforms.
  • Adhesion assays using modified TIL1 cells and COS7 cells transfected with CD44R1.
  • Monoclonal antibody blocking studies to identify binding determinants.

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Main Results:

  • Both CD44H and CD44R1 bind hyaluronan, but only CD44R1 promotes homotypic cellular aggregation in TIL1 cells.
  • CD44R1 recognizes a common determinant on both CD44H and CD44R1.
  • This determinant recognized by CD44R1 is located in a region distinct from the hyaluronan-binding site.

Conclusions:

  • CD44R1 possesses unique properties that promote cellular aggregation, independent of its hyaluronan-binding function.
  • The distinct binding determinant recognized by CD44R1 plays a crucial role in mediating cell-cell interactions.