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Binding of cell-surface expressed CD44 to hyaluronate is dependent on splicing and cell type

R van der Voort1, E Manten-Horst, L Smit

  • 1Department of Pathology, University of Amsterdam, The Netherlands.

Biochemical and Biophysical Research Communications
|September 5, 1995
PubMed

Insights

The standard CD44 protein (CD44s) mediates cell binding to hyaluronate (HA), but certain variants generated by alternative RNA splicing do not. Cell type also influences CD44

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • CD44 is a key cell-surface receptor mediating cell interactions with hyaluronate (HA).
  • Alternative RNA splicing generates numerous CD44 variants with potentially diverse functions.
  • Understanding CD44 variant function is crucial for cell adhesion and signaling research.

Purpose of the Study:

  • To investigate the impact of CD44 alternative splicing on cell binding to HA.
  • To compare the HA-binding capabilities of different CD44 isoforms in distinct cell types.
  • To elucidate the regulatory mechanisms governing CD44-mediated cell adhesion.

Main Methods:

  • Transfection of CD44-negative Namalwa and COS7 cell lines with different CD44 isoforms (CD44s, CD44v3-10, CD44v8-10).
  • Assessing cell adhesion to immobilized and soluble hyaluronate (HA).
  • Stimulation of CD44 receptor using activating anti-CD44 monoclonal antibody (mAb) and phorbol ester.

Main Results:

  • CD44 standard form (CD44s) mediated HA binding in Namalwa cells, while CD44v3-10 and CD44v8-10 isoforms did not.
  • Stimulation significantly increased HA binding for CD44s compared to other isoforms in Namalwa cells.
  • In contrast, COS7 cells exhibited similar HA binding across all tested CD44 isoforms (CD44s, CD44v8-v10, CD44v3-v10).

Conclusions:

  • Alternative splicing of CD44 influences its ability to bind hyaluronate (HA) in a cell-type-specific manner.
  • The standard CD44 isoform (CD44s) is more effective at mediating HA binding than certain spliced variants.
  • Both CD44 splicing and the cellular context are critical determinants of CD44-mediated cell adhesion to HA.

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