Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 17, Issue 12, Pages 5390-5399Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.e06-08-0740
Keywords
-
Categories
Funding
- NIAMS NIH HHS [AR40994, R01 AR040994] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available