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)6275-6287
Number of pages13
JournalJournal of Cell Science
Volume117
Issue number26
DOIs
Publication statusPublished - Dec 15 2004

Fingerprint

Metalloproteases
Lipids
Membranes
Detergents
Furin
Physiological Phenomena
Cell Line
Golgi Apparatus
Pathologic Processes
Cell Movement
Melanoma
Peptide Hydrolases
Cell Membrane
Growth

Keywords

  • Cell invasion
  • Extracellular matrix
  • Intracellular trafficking
  • Matrix metalloproteases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Mazzone, M., Baldassarre, M., Beznoussenko, G., Giacchetti, G., Cao, J., Zucker, S., ... Buccione, R. (2004). Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains. Journal of Cell Science, 117(26), 6275-6287. https://doi.org/10.1242/jcs.01563

Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains. / Mazzone, Marco; Baldassarre, Massimiliano; Beznoussenko, Galina; Giacchetti, Giada; Cao, Jian; Zucker, Stanley; Luini, Alberto; Buccione, Roberto.

In: Journal of Cell Science, Vol. 117, No. 26, 15.12.2004, p. 6275-6287.

Research output: Contribution to journalArticle

Mazzone, M, Baldassarre, M, Beznoussenko, G, Giacchetti, G, Cao, J, Zucker, S, Luini, A & Buccione, R 2004, 'Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains', Journal of Cell Science, vol. 117, no. 26, pp. 6275-6287. https://doi.org/10.1242/jcs.01563
Mazzone, Marco ; Baldassarre, Massimiliano ; Beznoussenko, Galina ; Giacchetti, Giada ; Cao, Jian ; Zucker, Stanley ; Luini, Alberto ; Buccione, Roberto. / Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains. In: Journal of Cell Science. 2004 ; Vol. 117, No. 26. pp. 6275-6287.
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