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First published online 23 November 2004
doi: 10.1242/jcs.01563

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

¹ Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro, 66030, Chieti, Italy
² Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
³ Department of Veterans Affairs Medical Center, Northport, NY 11768, USA

^* Author for correspondence (e-mail: buccione{at}negrisud.it)

Accepted 24 September 2004

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.

Key words: Matrix metalloproteases, Intracellular trafficking, Extracellular matrix, Cell invasion

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