Both Drosophila matrix metalloproteinases have released and membrane-tethered forms but have different substrates.
Both Drosophila matrix metalloproteinases have released and membrane-tethered forms but have different substrates.
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DOI：
10.1038/srep44560
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发表时间：
2017-03-16
影响因子：
4.6
通讯作者：
Page-McCaw A
中科院分区：
文献类型：
--
作者：
LaFever KS;Wang X;Page-McCaw P;Bhave G;Page-McCaw A
基质金属蛋白酶（MMP）是一种细胞外蛋白酶，可以切割细胞外基质并改变信号通路。它们与许多疾病状态有关，但很难理解单个MMPs的贡献，因为脊椎动物中有超过20种MMPs。脊椎动物MMPs具有重叠底物，它们表现出遗传冗余和补偿，并且药理学抑制剂是非特异性的。相比之下，果蝇中只有两个MMP基因，DmMmp1和DmMmp2，这使得果蝇成为分析MMP特异性基础的有吸引力的系统。以前，果蝇MMPs已被归类为他们的细胞周围的定位，Mmp1似乎是分泌和Mmp2似乎是膜锚定，这表明蛋白质定位是在这个小MMP家族的关键区别。我们在这里报告，这两个基因的产品被发现在细胞表面和媒体释放。此外，我们发现这两种基因的产物都含有GPI锚定物，并且出乎意料的是，当GPI锚定的MMP失活时，它们会促进细胞粘附。最后，通过使用新的试剂和检测，我们表明，这两种MMP切割不同的底物，这表明这是这个最小的MMP家族的重要区别。
Matrix metalloproteinases (MMPs) are extracellular proteases that can cleave extracellular matrix and alter signaling pathways. They have been implicated in many disease states, but it has been difficult to understand the contribution of individual MMPs, as there are over 20 MMPs in vertebrates. The vertebrate MMPs have overlapping substrates, they exhibit genetic redundancy and compensation, and pharmacological inhibitors are non-specific. In contrast, there are only two MMP genes in Drosophila, DmMmp1 and DmMmp2, which makes Drosophila an attractive system to analyze the basis of MMP specificity. Previously, Drosophila MMPs have been categorized by their pericellular localization, as Mmp1 appeared to be secreted and Mmp2 appeared to be membrane-anchored, suggesting that protein localization was the critical distinction in this small MMP family. We report here that products of both genes are found at the cell surface and released into media. Additionally, we show that products of both genes contain GPI-anchors, and unexpectedly, that GPI-anchored MMPs promote cell adhesion when they are rendered inactive. Finally, by using new reagents and assays, we show that the two MMPs cleave different substrates, suggesting that this is the important distinction within this smallest MMP family.