| First Author | Hara T | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 413 |
| Issue | 2 | Pages | 277-81 |
| PubMed ID | 21893028 | Mgi Jnum | J:177526 |
| Mgi Id | MGI:5295343 | Doi | 10.1016/j.bbrc.2011.08.085 |
| Citation | Hara T, et al. (2011) Genetic dissection of proteolytic and non-proteolytic contributions of MT1-MMP to macrophage invasion. Biochem Biophys Res Commun 413(2):277-81 |
| abstractText | MT1-MMP/MMP-14 is a major invasion-promoting membrane protease expressed in macrophages. In addition to its proteolytic activity that degrades the extracellular matrix, MT1-MMP also boosts ATP production in cells in a manner independent of its proteolytic activity. It remains unclear to what extent the proteolytic and energy-boosting activities of MT1-MMP contribute to macrophage invasion. Recently, we demonstrated that the cytoplasmic tail of MT1-MMP makes use of APBA3/Mint3 to activate HIF-1 and thereby boosts glycolysis for ATP production. Here, we used Apba3(-/-) macrophages to dissect the contribution of the proteolytic and the energy-boosting activities of MT1-MMP. The proteolytic activity of MT1-MMP was not affected by the lack of APBA3 in macrophages. Apba3(-/-) and Mmp14(-/-) macrophages exhibited a 55% reduction of ATP levels compared to wild-type (WT) cells and the rate of motility of the mutant cells was accordingly reduced. In contrast, matrigel invasion by Mmp14(-/-) and Apba3(-/-) macrophages was reduced to 24% and 55.4%, respectively, of the level observed in WT cells. These results represent the first attempt to dissect the contribution of the two invasion-promoting activities of MT1-MMP to macrophage invasion. |
