| First Author | Sakamoto T | Year | 2009 |
| Journal | Genes Cells | Volume | 14 |
| Issue | 5 | Pages | 617-26 |
| PubMed ID | 19371380 | Mgi Jnum | J:158339 |
| Mgi Id | MGI:4438561 | Doi | 10.1111/j.1365-2443.2009.01293.x |
| Citation | Sakamoto T, et al. (2009) Cytoplasmic tail of MT1-MMP regulates macrophage motility independently from its protease activity. Genes Cells 14(5):617-26 |
| abstractText | Membrane type-1 matrix metalloproteinase (MT1-MMP) is a proinvasive protease that regulates various cellular functions as evidenced by myriad defects in different types of cells and tissues in MT1-MMP-deficient (MT1(-/-)) mice. Here we demonstrate that MT1(-/-) mice exhibit fewer infiltrating macrophages into sites of inflammation. MT1(-/-)macrophages exhibited a reduced ability to invade reconstituted basement membrane (Matrigel) and invasion by wild type (WT) macrophages was inhibited by a synthetic MMP inhibitor (BB94) to a level similar to that of MT1(-/-) cells. The rate of migration of MT1(-/-) macrophages was also low compared to that of the WT cells and re-expression of MT1-MMP in MT1(-/-) macrophages reconstituted their migratory activity. Unexpectedly, however, BB94 did not inhibit the migration of WT macrophages. The migration-boosting activity of MT1-MMP is retained in a mutant that lacks most of the extracellular portion including the catalytic and hemopexin-like domains. In contrast, deletion of the cytoplasmic (CP) tail abolished the activity completely. Thus, we have demonstrated that MT1-MMP regulates macrophages via its invasion-promoting protease activity as well as its CP-dependent non-proteolytic activity to boost cell migration. |
