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MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

María Yañez-Mó1, Olga Barreiro, Pilar Gonzalo

  • 1Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.

Blood
|July 30, 2008
PubMed

Insights

Tetraspanin CD151 regulates membrane type 1 matrix metalloproteinase (MT1-MMP) activity in endothelial cells. CD151 deficiency impairs MT1-MMP

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Membrane type 1 matrix metalloproteinase (MT1-MMP) is crucial for endothelial function and angiogenesis.
  • MT1-MMP activity is regulated by its interactions with other cell surface molecules.

Purpose of the Study:

  • To investigate the molecular interactions regulating MT1-MMP function.
  • To elucidate the role of tetraspanin CD151 in MT1-MMP activity and endothelial homeostasis.

Main Methods:

  • Co-localization studies at endothelial cell junctions.
  • Biochemical assays and Förster Resonance Energy Transfer (FRET) analyses.
  • siRNA knockdown and analysis of MT1-MMP activity and collagen degradation.
  • Analysis of MT1-MMP localization and detergent-resistant membrane domains.

Main Results:

  • MT1-MMP forms ternary complexes with CD151 and alpha3beta1 integrin at lateral endothelial cell junctions.
  • CD151 knockdown enhances MT1-MMP-mediated MMP2 activation but diminishes collagen degradation.
  • CD151 deficiency affects MT1-MMP subcellular localization and its association with alpha3beta1 integrin.

Conclusions:

  • Tetraspanin CD151 plays a novel regulatory role in MT1-MMP collagenolytic activity via tetraspanin microdomains.
  • CD151 is a key regulator of MT1-MMP in maintaining endothelial homeostasis.

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