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Regulation of membrane-type matrix metalloproteinase 1 activity by dynamin-mediated endocytosis

A Jiang1, K Lehti, X Wang

  • 1Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 8, 2001
PubMed

Insights

Membrane-type matrix metalloproteinase 1 (MT1-MMP) activity is controlled by endocytosis. Concanavalin A shifts MT1-MMP to the cell surface, activating pro-MMP-2, while its cytoplasmic domain regulates this trafficking.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Membrane-type matrix metalloproteinase 1 (MT1-MMP) is crucial for extracellular matrix remodeling.
  • Mechanisms controlling cell surface MT1-MMP activity are not fully understood.

Purpose of the Study:

  • To investigate the role of endocytosis in regulating MT1-MMP activity.
  • To elucidate the mechanisms controlling MT1-MMP trafficking and activation.

Main Methods:

  • Used HT1080 cells and transfected cells expressing wild-type MT1-MMP and a cytoplasmic truncation mutant (MT1 Delta C).
  • Investigated the effect of Concanavalin A (Con A) on MT1-MMP localization and pro-MMP-2 activation.
  • Utilized immunofluorescence to assess colocalization with clathrin and endosomal antigen 1.
  • Examined the impact of dynamin K44A dominant-negative mutant on MT1-MMP activity.

Main Results:

  • Con A induced pro-MMP-2 activation by promoting MT1-MMP translocation to the cell surface.
  • MT1 Delta C showed enhanced cell surface expression and pro-MMP-2 activation, resistant to Con A.
  • MT1-MMP colocalized with clathrin and endosomes, indicating involvement in clathrin-mediated endocytosis.
  • Dynamin K44A expression elevated MT1-MMP activity, confirming dynamin-dependent endocytosis.

Conclusions:

  • MT1-MMP activity is regulated by dynamin-dependent endocytosis.
  • The cytoplasmic domain of MT1-MMP is critical for its trafficking and regulation by endocytosis.
  • Endocytosis controls MT1-MMP localization and extracellular matrix remodeling functions.

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