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Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein
Microsystems & Nanoengineering ( IF 7.3 ) Pub Date : 2020-06-29 , DOI: 10.1038/s41378-020-0147-1
Bin Cai 1 , Jie Liu 2 , Yunfei Zhao 3 , Xiangyu Xu 2 , Bing Bu 4 , Dechang Li 5 , Lei Zhang 6 , Wei Dong 3 , Baohua Ji 5, 7 , Jiajie Diao 1
Affiliation  

Although numerous studies have shown that the protein α-synuclein (α-Syn) plays a central role in Parkinson’s disease, dementia with Lewy bodies, and other neurodegenerative diseases, the protein’s physiological function remains poorly understood. Furthermore, despite recent reports suggesting that, under the influence of Ca2+, α-Syn can interact with synaptic vesicles, the mechanisms underlying that interaction are far from clear. Thus, we used single-vesicle imaging to quantify the extent to which Ca2+ regulates nanoscale vesicle clustering mediated by α-Syn. Our results revealed not only that vesicle clustering required α-Syn to bind to anionic lipid vesicles, but also that different concentrations of Ca2+ exerted different effects on how α-Syn induced vesicle clustering. In particular, low concentrations of Ca2+ inhibited vesicle clustering by blocking the electrostatic interaction between the lipid membrane and the N terminus of α-Syn, whereas high concentrations promoted vesicle clustering, possibly due to the electrostatic interaction between Ca2+ and the negatively charged lipids that is independent of α-Syn. Taken together, our results provide critical insights into α-Syn’s physiological function, and how Ca2+ regulates vesicle clustering mediated by α-Syn.



中文翻译:

单囊泡成像量化钙对α-突触核蛋白介导的纳米级囊泡聚集的调节

尽管大量研究表明蛋白质 α-突触核蛋白 (α-Syn) 在帕金森病、路易体痴呆和其他神经退行性疾病中起着核心作用,但对该蛋白质的生理功能仍知之甚少。此外,尽管最近的报道表明,在 Ca 2+的影响下,α-Syn 可以与突触小泡相互作用,但这种相互作用的机制尚不清楚。因此,我们使用单囊泡成像来量化 Ca 2+调节由 α-Syn 介导的纳米级囊泡聚集的程度。我们的结果表明,不仅囊泡聚集需要 α-Syn 与阴离子脂质囊泡结合,而且不同浓度​​的 Ca 2+对α-Syn 如何诱导囊泡聚集产生不同的影响。特别是,低浓度的 Ca 2+通过阻断脂质膜和 α-Syn N 末端之间的静电相互作用来抑制囊泡聚集,而高浓度促进了囊泡聚集,这可能是由于 Ca 2+和负离子之间的静电相互作用。不依赖于 α-Syn 的带电脂质。总之,我们的结果提供了对 α-Syn 生理功能以及 Ca 2+如何调节由 α-Syn 介导的囊泡聚集的重要见解。

更新日期:2020-06-29
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