Membrane type I-matrix metalloproteinase (MT1-MMP) is internalised by two different pathways and is recycled to the cell surface.
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.
Remacle
Albert
A
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Murphy
Gillian
G
Roghi
Christian
C
D021941:Caveolae / Q000201:enzymology*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000201:enzymology*; D002784:Cholesterol / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000201:enzymology*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019716:Tissue Inhibitor of Metalloproteinase-2; D002784:Cholesterol; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases