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Membrane type I-matrix metalloproteinase (MT1-MMP) is internalised by two different pathways and is recycled to the
Albert Remacle1, Gillian Murphy, Christian Roghi
1School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Abstract:
Membrane type 1-matrix metalloproteinase (MT1-MMP) is an integral type I transmembrane multidomain zinc-dependent endopeptidase involved in extracellular matrix remodelling in physiological as well as pathological processes. MT1-MMP participates in the regulated turnover of various extracellular matrix components as well as the activation of secreted metalloproteinases and the cleavage of various cell membrane components. MT1-MMP expression has been reported to correlate with the malignancy of various tumour types and is thought to be an important mediator of cell migration and invasion. Recently, it has been proposed that internalisation of the enzyme from the cell surface is a major short-term level of MT1-MMP regulation controlling the net amount of active enzyme present at the plasma membrane. In this paper we show that, in HT1080 fibrosarcoma cells, MT1-MMP is internalised from the cell surface and colocalises with various markers of the endocytic compartment. Interestingly, we observed that in these cells, internalisation occurs by a combination of both clathrin-mediated and -independent pathways, most probably involving caveolae. In addition, internalised MT1-MMP is recycled to the cell surface, which could, in addition to downregulation of the enzymatic activity, represent a rapid response mechanism used by the cell for relocalising active MT1-MMP at the leading edge during migration.
Insights
Membrane type 1-matrix metalloproteinase (MT1-MMP) is internalized from the cell surface in fibrosarcoma cells. This enzyme recycles back to the cell surface, regulating migration and invasion.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Membrane type 1-matrix metalloproteinase (MT1-MMP) is a key enzyme in extracellular matrix remodeling.
- MT1-MMP is implicated in tumor malignancy, cell migration, and invasion.
- Cell surface internalization is a proposed regulatory mechanism for MT1-MMP activity.
Purpose of the Study:
- To investigate the internalization pathways of MT1-MMP in HT1080 fibrosarcoma cells.
- To determine if internalized MT1-MMP is recycled to the cell surface.
- To understand the role of MT1-MMP internalization and recycling in cell migration.
Main Methods:
- Confocal microscopy to track MT1-MMP localization.
- Colocalization studies with endocytic markers.
- Analysis of MT1-MMP internalization and recycling dynamics.
Main Results:
- MT1-MMP is internalized from the cell surface in HT1080 fibrosarcoma cells.
- Internalization occurs via both clathrin-mediated and clathrin-independent pathways, likely involving caveolae.
- Internalized MT1-MMP is recycled back to the cell surface.
Conclusions:
- MT1-MMP internalization and recycling represent a rapid regulatory mechanism for controlling active enzyme levels at the plasma membrane.
- This dynamic process is crucial for MT1-MMP relocalization during cell migration.
- Understanding MT1-MMP trafficking is vital for targeting its role in cancer progression.