Invasion by activated macrophages requires delivery of nascent membrane‐type‐1 matrix metalloproteinase through late endosomes/lysosomes to the cell surface

• DOI: 10.1111/tra.12675
• Publication Date: 2019-07-12T07:48:27Z
• Authors: Joan Röhl; Zoe E. West; Maren Rudolph; Andreea Zaharia; Derek Van Lonkhuyzen; Danica K. Hickey; Annalese B. T. Se...; Rachael Z. Murray
• Keywords: 0301 basic medicine; late endosome; Macrophage; VAMP7; Golgi Apparatus; VAMP8; Endosomes; R-SNARE Proteins; Mice; 03 medical and health sciences; Cell Movement; MT1-MMP; 616; Matrix Metalloproteinase 14; Animals; Qc-SNARE Proteins; MMP14; Cell Membrane; Macrophage Activation; Qb-SNARE Proteins; secretion; Protein Transport; RAW 264.7 Cells; SNARE; lysosome; Lysosomes

Macrophage migration into injured or infected tissue is a key aspect in the pathophysiology of many diseases where inflammation driving factor. Membrane-type-1 matrix metalloproteinase (MT1-MMP) cleaves extracellular components to facilitate invasion. Here we show that, unlike constitutive MT1-MMP surface recycling seen cancer cells, unactivated macrophages express low levels MT1-MMP. Upon lipopolysaccharide (LPS) activation, synthesis dramatically increases 10-fold at by 15 hours. trafficked from Golgi complex via late endosomes/lysosomes pathway regulated endosome/lysosome R-SNAREs VAMP7 and VAMP8. These form two separate complexes with Q-SNARE Stx4/SNAP23 regulate delivery plasma membrane. Loss either one these SNAREs leads reduction MT1-MMP, gelatinase activity reduced Thus, inhibiting transport through this could reduce macrophage resulting inflammation.