Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, 20246 Hamburg, Germany.
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, 20246 Hamburg, Germany.
Biochim Biophys Acta Mol Cell Res. 2022 Apr;1869(4):119189. doi: 10.1016/j.bbamcr.2021.119189. Epub 2021 Dec 29.
Matrix metalloproteinases are a family of zinc-dependent endopeptidases that are involved in a large variety of proteolytic processes in physiological and pathological scenarios, including immune cell surveillance, tissue homeostasis, or tumor cell metastasis. This is based on their ability to cleave a plethora of substrates that include components of the extracellular matrix, but also cell surface-associated and intracellular proteins. Accordingly, a tight regulatory web has evolved that closely regulates spatiotemporal activity of specific MMPs. An often underappreciated mechanism of MMP regulation involves their trafficking to and from specific subcellular sites that require MMP activity only for a certain period. In this review, we focus on the current knowledge of MMP intracellular trafficking, their secretion or surface exposure, as well as their recycling back from the cell surface. We discuss molecular mechanisms that enable these steps, in particular microtubule-dependent motility of vesicles that is driven by molecular motors and directed by vesicle regulatory proteins. Finally, we also point out open questions in the field of MMP motility that may become important in the future.
基质金属蛋白酶是一类锌依赖性内肽酶，参与生理和病理情况下的多种蛋白水解过程，包括免疫细胞监视、组织动态平衡或肿瘤细胞转移。这是基于它们能够切割大量底物的能力，这些底物包括细胞外基质的成分，以及细胞表面相关和细胞内蛋白。因此，已经进化出一个紧密的调节网络，以密切调节特定 MMP 的时空活性。MMP 调节的一个经常被低估的机制涉及它们向特定亚细胞位点的运输和从特定亚细胞位点的运输，这些亚细胞位点仅在特定时间段内需要 MMP 活性。在这篇综述中，我们重点介绍 MMP 细胞内运输、它们的分泌或表面暴露以及从细胞表面再循环的最新知识。我们讨论了使这些步骤成为可能的分子机制，特别是由分子马达驱动并由囊泡调节蛋白指导的囊泡的微管依赖性运动。最后，我们还指出了 MMP 运动领域的一些悬而未决的问题，这些问题在未来可能会变得很重要。
