Linder Stefan, Scita Giorgio
a Institute for Medical Microbiology; Virology and Hygiene ; University Medical Center Eppendorf ; Hamburg , Germany.
Small GTPases. 2015;6(3):145-52. doi: 10.4161/21541248.2014.985484. Epub 2015 Jun 24.
The matrix metalloproteinase MT1-MMP is a central regulator of cell invasion in both physiological and pathological settings, such as tissue surveillance by immune cells and cancer cell metastasis. MT1-MMP cleaves a plethora of intra- and extracellular proteins, including extracellular matrix proteins, matrix receptors, and also other MMPs, and thus enables modification of both the cell surface proteome and the pericellular environment. Despite its importance for cell invasion, the pathways regulating MT1-MMP exposure on the cell surface are largely unknown. Recently, our groups discovered that a specific subset of RABGTPases, most notably RAB5a, is critical for MT1-MMP trafficking in primary human macrophages and carcinoma cells. Here, we discuss and contrast our findings for both cell types, pointing out common features and differences in the RABGTPase-dependent trafficking of MT1-MMP in health and disease.
基质金属蛋白酶MT1-MMP是生理和病理环境中细胞侵袭的核心调节因子，如免疫细胞的组织监测和癌细胞转移。MT1-MMP可切割大量细胞内和细胞外蛋白质，包括细胞外基质蛋白、基质受体以及其他MMP，从而实现对细胞表面蛋白质组和细胞周围环境的修饰。尽管MT1-MMP对细胞侵袭很重要，但其在细胞表面暴露的调控途径在很大程度上尚不清楚。最近，我们的团队发现，RABGTPases的一个特定亚群，尤其是RAB5a，对原代人巨噬细胞和癌细胞中MT1-MMP的运输至关重要。在此，我们讨论并对比了两种细胞类型的研究结果，指出了健康和疾病状态下RABGTPase依赖的MT1-MMP运输的共同特征和差异。
