Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains

Marco Mazzone, Massimiliano Baldassarre, Galina Beznoussenko, Giada Giacchetti, Jian Cao, Stanley Zucker, Alberto Luini, Roberto Buccione

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The integral membrane type 1 matrix metalloprotease (MT1-MMP) is a pivotal protease in a number of physiological and pathological processes and confers both non-tumorigenic and tumorigenic cell lines with a specific growth advantage in a three-dimensional matrix. Here we show that, in a melanoma cell line, the majority (80%) of MT1-MMP is sorted to detergent-resistant membrane fractions; however, it is only the detergent-soluble fraction (20%) of MT1-MMP that undergoes intracellular processing to the mature form. Also, this processed MT1-MMP is the sole form responsible for ECM degradation in vitro. Finally, furin-dependent processing of MT1-MMP is shown to occur intracellularly after exit from the Golgi apparatus and prior to its arrival at the plasma membrane. It is thus proposed that the association of MT1-MMP with different membrane subdomains might be crucial in the control of its different activities: for instance in cell migration and invasion and other less defined ones such as MT1-MMP-dependent signaling pathways.

Original languageEnglish
Pages (from-to)6275-87
Number of pages13
JournalJournal of Cell Science
Volume117
Issue numberPt 26
DOIs
Publication statusPublished - 15 Dec 2004

Keywords

  • Biotinylation
  • Cell Compartmentation
  • Cell Line, Tumor
  • Cell Movement
  • Enzyme Activation
  • Extracellular Matrix
  • Fluorescent Antibody Technique
  • Furin
  • Green Fluorescent Proteins
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinases, Membrane-Associated
  • Melanoma
  • Metalloendopeptidases
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Protein Transport

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