VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.

VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.
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DOI:
10.3389/fcell.2022.895856
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发表时间:
2022
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
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--
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囊泡相关膜蛋白(VAMP)相关蛋白(VAPs)是真核细胞中普遍存在的内质网末端锚定的膜蛋白。它们的N端主要精子蛋白(MSP)结构域面向胞浆,使它们能够与多种细胞蛋白相互作用。因此,VAP蛋白在许多细胞过程中都是至关重要的,包括细胞器膜系留、脂质转移、自噬、离子稳态和病毒防御。在这里,我们及时提供了VAPA/B结合伙伴数量增加的概述,并讨论了VAPA/B在维持细胞器-内质网相互作用和合作中的作用。此外,我们还讨论了病毒和细胞内细菌如何劫持VAP及其结合伙伴,以诱导宿主ER和含有病原体的间隔之间的相互作用,并支持病原体复制。最后,我们关注VAP在人类疾病中的作用,并讨论VAPB突变是如何导致细胞内稳态的破坏和导致肌萎缩侧索硬化症的。
Vesicle-associated membrane protein (VAMP)-associated proteins (VAPs) are ubiquitous ER-resident tail-anchored membrane proteins in eukaryotic cells. Their N-terminal major sperm protein (MSP) domain faces the cytosol and allows them to interact with a wide variety of cellular proteins. Therefore, VAP proteins are vital to many cellular processes, including organelle membrane tethering, lipid transfer, autophagy, ion homeostasis and viral defence. Here, we provide a timely overview of the increasing number of VAPA/B binding partners and discuss the role of VAPA/B in maintaining organelle-ER interactions and cooperation. Furthermore, we address how viruses and intracellular bacteria hijack VAPs and their binding partners to induce interactions between the host ER and pathogen-containing compartments and support pathogen replication. Finally, we focus on the role of VAP in human disease and discuss how mutated VAPB leads to the disruption of cellular homeostasis and causes amyotrophic lateral sclerosis.
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