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 language | English |
|---|---|
| Pages (from-to) | 6275-6287 |
| Number of pages | 13 |
| Journal | Journal of Cell Science |
| Volume | 117 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - Dec 15 2004 |
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Keywords
- Cell invasion
- Extracellular matrix
- Intracellular trafficking
- Matrix metalloproteases
ASJC Scopus subject areas
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains
AU - Mazzone, Marco
AU - Baldassarre, Massimiliano
AU - Beznoussenko, Galina
AU - Giacchetti, Giada
AU - Cao, Jian
AU - Zucker, Stanley
AU - Luini, Alberto
AU - Buccione, Roberto
PY - 2004/12/15
Y1 - 2004/12/15
N2 - 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.
AB - 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.
KW - Cell invasion
KW - Extracellular matrix
KW - Intracellular trafficking
KW - Matrix metalloproteases
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UR - http://www.scopus.com/inward/citedby.url?scp=13444310742&partnerID=8YFLogxK
U2 - 10.1242/jcs.01563
DO - 10.1242/jcs.01563
M3 - Article
C2 - 15561768
AN - SCOPUS:13444310742
VL - 117
SP - 6275
EP - 6287
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 26
ER -