Membrane type I-matrix metalloproteinase (MT1-MMP) is internalised by two different pathways and is recycled to the cell surface
Membrane type I-matrix metalloproteinase (MT1-MMP) is internalised by two different pathways and is recycled to the cell surface
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DOI：
10.1242/jcs.00710
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发表时间：
2003-10-01
影响因子：
4
通讯作者：
Roghi, C
中科院分区：
文献类型：
--
作者：
Remacle, A;Murphy, G;Roghi, C
膜1型基质金属蛋白酶（MT 1-MMP）是一种整合的I型跨膜多结构域锌依赖性内肽酶，参与生理和病理过程中的细胞外基质重塑。MT 1-MMP参与调节各种细胞外基质成分的周转以及分泌的金属蛋白酶的活化和各种细胞膜成分的裂解。MT 1-MMP的表达与多种肿瘤的恶性程度相关，并被认为是细胞迁移和侵袭的重要介质。最近，已经提出，从细胞表面的酶的内化是MT 1-MMP调节的主要短期水平，其控制存在于质膜上的活性酶的净量。在本文中，我们表明，在HT 1080纤维肉瘤细胞，MT 1-MMP是从细胞表面和colocalises与各种标志物的内吞隔室内化。有趣的是，我们观察到，在这些细胞中，内化发生的网格蛋白介导的和独立的途径的组合，最有可能涉及小窝。此外，内化的MT 1-MMP被再循环至细胞表面，除了下调酶活性之外，这可能代表细胞在迁移期间用于在前沿重新定位活性MT 1-MMP的快速反应机制。
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.