UK Dementia Research Institute at King's College London, The Maurice Wohl Institute, London, UK.
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Centre, GA Nijmegen, Netherlands.
J Biol Chem. 2021 Jan-Jun;296:100421. doi: 10.1016/j.jbc.2021.100421. Epub 2021 Feb 18.
Intracellular organelles do not, as thought for a long time, act in isolation but are dynamically tethered together by entire machines responsible for interorganelle trafficking and positioning. Among the proteins responsible for tethering is the family of VAMP-associated proteins (VAPs) that appear in all eukaryotes and are localized primarily in the endoplasmic reticulum. The major functional role of VAPs is to tether the endoplasmic reticulum with different organelles and regulate lipid metabolism and transport. VAPs have gained increasing attention because of their role in human pathology where they contribute to infections by viruses and bacteria and participate in neurodegeneration. In this review, we discuss the structure, evolution, and functions of VAPs, focusing more specifically on VAP-B for its relationship with amyotrophic lateral sclerosis and other neurodegenerative diseases.
细胞内细胞器并非像长期以来人们认为的那样孤立地发挥作用，而是通过负责细胞器间运输和定位的完整机器动态地连接在一起。负责连接的蛋白质之一是 VAMP 相关蛋白 (VAP) 家族，它存在于所有真核生物中，主要定位于内质网。VAP 的主要功能是将内质网与不同的细胞器连接起来，并调节脂质代谢和运输。由于 VAP 在人类病理学中的作用，它们有助于病毒和细菌的感染，并参与神经退行性变，因此引起了越来越多的关注。在这篇综述中，我们讨论了 VAP 的结构、进化和功能，特别关注 VAP-B 与其与肌萎缩侧索硬化症和其他神经退行性疾病的关系。
