The trans-SNARE complex VAMP4/Stx6/Stx7/Vti1b is a key regulator of Golgi to late endosome MT1-MMP transport in macrophages.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Traffic Pub Date : 2021-11-01 Epub Date: 2021-09-13 DOI:10.1111/tra.12813

Zoe Elizabeth West, Savannah Margaret Aitcheson, Annalese Barbara Trudy Semmler, Rachael Zoe Murray

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引用次数: 3

Abstract

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.

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跨snare复合物VAMP4/Stx6/Stx7/Vti1b是巨噬细胞中高尔基体到晚期核内体MT1-MMP运输的关键调节因子。

基质金属蛋白酶(matrix metalloproteinase, 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，而这需要在细胞表面，它们才能降解致密的细胞外基质(ECM)成分，从而创造一条迁移到受伤和感染组织的路径。固定和实时成像显示，新制造的MT1-MMP被包装成囊泡，在通往表面的途中与LBPA+ LAMP1+晚期核内体交通并融合。R-SNARE VAMP4存在于高尔基衍生囊泡中，与Q-SNARE复合体Stx6/Stx7/Vti1b形成跨snare复合体。Stx6/Stx7/Vti1b复合物已被证明在脂多糖(LPS)激活的细胞中上调，通过经典途径增加关键细胞因子的运输，现在我们在这里显示它的上调也在MT1-MMP运输的内体晚期途径中发挥作用。该复合物中任何SNAREs的消耗都减少了表面MT1-MMP和明胶的降解。相反，Stx6/Stx7/Vti1b组分的过表达会增加表面MT1-MMP水平。这表明Stx6/Stx7/Vti1b是免疫应答过程中巨噬细胞中一个关键的Q-SNARE复合物，并与VAMP4合作调节新生成的MT1-MMP的运输。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.