| Autor: |
Rohl, Joan, West, Zoe E., Rudolph, Maren, Zaharia, Andreea, Van Lonkhuyzen, Derek R., Hickey, Danica K., Semmler, Annalese B.T., Murray, Rachael Z. |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Traffic |
| ISSN: |
2381-3652 |
| Popis: |
Macrophage migration into injured or infected tissue is a key aspect in the pathophysiology of many diseases where inflammation is a driving factor. Membrane-type-1 matrix metalloproteinase (MT1-MMP) cleaves extracellular matrix components to facilitate invasion. Here we show that, unlike the constitutive MT1-MMP surface recycling seen in cancer cells, unactivated macrophages express low levels of MT1-MMP. Upon lipopolysaccharide (LPS) activation, MT1-MMP synthesis dramatically increases 10-fold at the surface by 15 h. MT1-MMP is trafficked from the Golgi complex to the surface via late endosomes/lysosomes in a pathway regulated by the late endosome/lysosome R-SNAREs VAMP7 and VAMP8. These form 2 separate complexes with the surface Q-SNARE complex Stx4/SNAP23 to regulate MT1-MMP delivery to the plasma membrane. Loss of either one of these SNAREs leads to a reduction in surface MT1-MMP, gelatinase activity and reduced invasion. Thus, inhibiting MT1-MMP transport through this pathway would reduce macrophage migration and the resulting inflammation. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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