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Endocytosis of ECM fibronectin is regulated by \u03b21 integrins, including \u03b15\u03b21 integrin. We have examined the role of extracellular proteases in regulating ECM fibronectin turnover. Our data show that membrane type matrix metalloproteinase 1 (MT1-MMP; also known as MMP14) is a crucial regulator of fibronectin turnover. Cells lacking MT1-MMP show reduced turnover and endocytosis of ECM fibronectin. MT1-MMP regulates ECM fibronectin remodeling by promoting extracellular cleavage of fibronectin and by regulating \u03b15\u03b21-integrin endocytosis. Our data also show that fibronectin polymerization stabilizes fibronectin fibrils and inhibits ECM fibronectin endocytosis by inhibiting \u03b15\u03b21-integrin endocytosis. These data are the first to show that an ECM protein and its modifying enzyme can regulate integrin endocytosis. These data also show that integrin trafficking plays a major role in modulating ECM fibronectin remodeling. The dual dependence of ECM fibronectin turnover on extracellular proteolysis and endocytosis highlights the complex regulatory mechanisms that control ECM remodeling to ensure maintenance of proper tissue function.<\/jats:p>","DOI":"10.1242\/jcs.087858","type":"journal-article","created":{"date-parts":[[2011,12,9]],"date-time":"2011-12-09T05:05:08Z","timestamp":1323407108000},"page":"4039-4050","source":"Crossref","is-referenced-by-count":120,"title":["MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin"],"prefix":"10.1242","volume":"124","author":[{"given":"Feng","family":"Shi","sequence":"first","affiliation":[{"name":"Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box CVRI, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Sottile","sequence":"additional","affiliation":[{"name":"Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box CVRI, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520384317300_R1","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1182\/blood-2007-09-112268","article-title":"PGE2 induces angiogenesis via MT1-MMP-mediated activation of the TGFbeta\/Alk5 signaling pathway","volume":"112","author":"Alfranca","year":"2008","journal-title":"Blood"},{"key":"2021042520384317300_R2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0049-0172(00)80012-8","article-title":"Fibronectin fragments and their role in inflammatory arthritis","volume":"29","author":"Barilla","year":"2000","journal-title":"Semin. 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