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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.

Original publication

DOI

10.1091/mbc.E06-08-0740

Type

Journal article

Journal

Mol Biol Cell

Publication Date

12/2006

Volume

17

Pages

5390 - 5399

Keywords

Animals, COS Cells, Cell Membrane, Cercopithecus aethiops, Collagen Type I, Collagenases, Dimerization, Dogs, Gels, Humans, Matrix Metalloproteinase 13, Matrix Metalloproteinase 14, Membrane Proteins, Mutant Proteins, Protein Structure, Tertiary, Recombinant Proteins