The activity of the matrix metalloproteinase (MMP) MT1-MMP is strictly regulated by expression and cellular location. In macrophages LPS activation leads to the up-regulation of MT1-MMP and this need to be at the cell surface for them to degrade the dense extracellular matrix (ECM) components to create a path to migrate into injured and infected tissues. Fixed and live imaging shows newly made MT1-MMP is packaged into vesicles that traffic to and fuse with LBPA⁺LAMP1⁺ late endosomes en route to the surface. The R-SNARE VAMP4, found on Golgi-derived vesicles that traffic to late endosomes, forms a trans-SNARE complex with the Q-SNARE complex Stx6/Stx7/Vti1b. The Stx6/Stx7/Vti1b complex has been shown to be up-regulated in lipopolysaccharide (LPS)-activated cells to increase trafficking of key cytokines through the classical pathway and now we show here it is up-regulation also plays a role in the late endosomal pathway of MT1-MMP trafficking. Depletion of any of the SNAREs in this complex reduces surface MT1-MMP and gelatin degradation. Conversely, overexpression of the Stx6/Stx7/Vti1b components increases surface MT1-MMP levels. This suggests that Stx6/Stx7/Vti1b is a key Q-SNARE complex in macrophages during an immune response and in partnership with VAMP4 it regulates transport of newly made MT1-MMP.

中文翻译：

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trans-SNARE 复合物 VAMP4/Stx6/Stx7/Vti1b 是高尔基体对巨噬细胞晚期内体 MT1-MMP 转运的关键调节因子

基质金属蛋白酶 (MMP) MT1-MMP 的活性受到表达和细胞定位的严格调控。在巨噬细胞中，LPS 激活导致 MT1-MMP 的上调，这需要在细胞表面使它们降解致密的细胞外基质 (ECM) 成分，从而形成迁移到受伤和感染组织中的途径。固定和实时成像显示新制造的 MT1-MMP 被包装成囊泡，在途中运输并与 LBPA ⁺ LAMP1 ⁺晚期内体融合到表面。R-SNARE VAMP4 发现于高尔基体衍生的囊泡上，该囊泡运输到晚期内体，与 Q-SNARE 复合体 Stx6/Stx7/Vti1b 形成反式 SNARE 复合体。Stx6/Stx7/Vti1b 复合物已被证明在脂多糖 (LPS) 激活的细胞中被上调，以通过经典途径增加关键细胞因子的运输，现在我们在这里证明它在晚期也发挥作用MT1-MMP 运输的内体途径。该复合物中任何 SNARE 的消耗都会减少表面 MT1-MMP 和明胶降解。相反，Stx6/Stx7/Vti1b 成分的过度表达会增加表面 MT1-MMP 水平。这表明 Stx6/Stx7/Vti1b 是免疫反应期间巨噬细胞中的关键 Q-SNARE 复合物，它与 VAMP4 合作调节新制造的 MT1-MMP 的转运。