Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs
Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs
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DOI：
10.1083/jcb.201907058
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发表时间：
2020-08-03
影响因子：
7.8
通讯作者：
von Blume, Julia
中科院分区：
文献类型：
--
作者：
Pacheco-Fernandez, Natalia;Pakdel, Mehrshad;von Blume, Julia
基质金属蛋白酶 (MMP) 可降解多种 ECM 成分，是细胞侵袭和组织组织的重要调节剂。尽管关于它们在健康和疾病中重塑 ECM 的功能已有很多报道，但它们在高尔基体中的运输仍然知之甚少。在此，我们报道顺式高尔基体蛋白 nucleobindin-1 (NUCB1) 对于沿高尔基体的 MMP2 和 MT1-MMP 运输至关重要。该过程是 Ca(2+) 依赖性的，是侵入性 MDA-MB-231 细胞迁移以及原代人巨噬细胞中明胶降解所必需的。我们的研究结果强调了 NUCB1 作为 MMP 运输重要组成部分的重要性及其对 ECM 重塑的总体影响。
Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca(2+)dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.