ECM regulates MT1-MMP localization with beta1 or alphavbeta3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells.
ECM regulates MT1-MMP localization with beta1 or alphavbeta3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells.
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DOI：
10.1083/jcb.200205026
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发表时间：
2002-11-11
期刊：
影响因子：
--
通讯作者：
Arroyo AG
中科院分区：
文献类型：
--
作者：
Gálvez BG;Matías-Román S;Yáñez-Mó M;Sánchez-Madrid F;Arroyo AG
研究了不同细胞外基质（ECMs）对人内皮细胞（ECs）的调节作用。首先，在β1整合素依赖性基质（如1型胶原（COL I）、纤维连接蛋白（FN）或纤维蛋白原（FG））上生长的融合ECs的细胞间接触处发现MT1-MMP，但在明胶（GEL）或玻璃体连接蛋白（VN）上没有发现。通过对转染MT1-MMP- gfp的ECs进行共聚焦视频显微镜观察，评估了细胞接触处MT1-MMP的新定位。此外，MT1-MMP在细胞间接触处与β1整合素共定位，而在迁移ec的运动相关结构上，它优先与αv - β3整合素共定位。此外，集束整合素招募MT1-MMP，中和抗β1或抗αv整合素单抗将MT1-MMP从其特定位点上取代，最终通过共免疫沉淀试验证明了这一生化关联。另一方面，COL I、FN或FG通过损害融合ECs上细胞表面MT1-MMP的内化而上调细胞表面MT1-MMP，而GEL或VN上的表达和内化没有改变。此外，在COL I、FN或FG上的融合ECs中，MT1-MMP活性降低。最后，MT1-MMP参与并协同β1和αvβ3整合素参与ECs在不同ECM上的迁移。这些数据显示了一种新的机制，通过ECM调节MT1-MMP与β1或αvβ3整合素在不同细胞区室的关联，从而调节其在人ECM上的内化、活性和功能。
Regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) by different extracellular matrices (ECMs) on human endothelial cells (ECs) has been investigated. First, MT1-MMP is found at the intercellular contacts of confluent ECs grown on β1 integrin–dependent matrix such as type 1 collagen (COL I), fibronectin (FN), or fibrinogen (FG), but not on gelatin (GEL) or vitronectin (VN). The novel localization of MT1-MMP at cell–cell contacts is assessed by confocal videomicroscopy of MT1-MMP-GFP–transfected ECs. Moreover, MT1-MMP colocalizes with β1 integrins at the intercellular contacts, whereas it is preferentially found with αvβ3 integrin at motility-associated structures on migrating ECs. In addition, clustered integrins recruit MT1-MMP and neutralizing anti-β1 or anti-αv integrin mAb displace MT1-MMP from its specific sites, pointing to a biochemical association that is finally demonstrated by coimmunoprecipitation assays. On the other hand, COL I, FN, or FG up-regulate cell surface MT1-MMP on confluent ECs by an impairment of its internalization, whereas expression and internalization are not modified on GEL or VN. In addition, MT1-MMP activity is diminished in confluent ECs on COL I, FN, or FG. Finally, MT1-MMP participates and cooperates with β1 and αvβ3 integrins in the migration of ECs on different ECM. These data show a novel mechanism by which ECM regulates MT1-MMP association with β1 or αvβ3 integrins at distinct cellular compartments, thus modulating its internalization, activity, and function on human ECs.
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影响因子：
7.8
作者：
Kajita, M;Itoh, Y;Chiba, T;Mori, H;Okada, A;Kinoh, H;Seiki, M
通讯作者：
Seiki, M
DOI：
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发表时间：
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期刊：
The Journal of cell biology
影响因子：
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作者：
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影响因子：
7.8
作者：
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通讯作者：
Simons, K
DOI：
10.1083/jcb.121.1.163
发表时间：
1993-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Cheresh DA
影响因子：
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作者：
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通讯作者：
Cheresh, DA