Cell surface collagenolysis requires homodimerization of the membrane-bound collagenase MT1-MMP

• Published in: Molecular biology of the cell Vol. 17; no. 12; pp. 5390 - 5399
• Main Authors: Itoh, Yoshifumi, Ito, Noriko, Nagase, Hideaki, Evans, Richard D, Bird, Sarah A, Seiki, Motoharu
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.12.2006
• Subjects: Animals; Cell Membrane - metabolism; Cercopithecus aethiops; Collagen Type I - metabolism; Collagenases - metabolism; COS Cells; Dimerization; Dogs; Gels; Humans; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase 14 - chemistry; Matrix Metalloproteinase 14 - metabolism; Membrane Proteins - metabolism; Mutant Proteins - metabolism; Protein Structure, Tertiary; Recombinant Proteins - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E06-08-0740

Pericellular degradation of interstitial collagens is a crucial event for cells to migrate through the dense connective tissue matrices, where collagens exist as insoluble fibers. A key proteinase that participates in this process is considered to be membrane-type 1 matrix metalloproteinase (MT1-MMP or MMP-14), but little is known about the mechanism by which it cleaves the insoluble collagen. Here we report that homodimerization of MT1-MMP through its hemopexin (Hpx) domain is essential for cleaving type I collagen fibers at the cell surface. When dimerization was blocked by coexpressing either a membrane-bound or a soluble form of the Hpx domain, cell surface collagenolytic activity was inhibited in a dose-dependent manner. When MMP-13, a soluble collagenase active as a monomer in solution, was expressed as a membrane-anchored form on the cell surface, homodimerization was also required to cleave collagen. Our results introduce a new concept in that pericellular collagenolysis is regulated by correct molecular assembly of the membrane-anchored collagenase, thereby governing the directionality of the cell to migrate in tissue.