Single-vesicle imaging quantifies calcium's regulation of nanoscale vesicle clustering mediated by α-synuclein.
Single-vesicle imaging quantifies calcium's regulation of nanoscale vesicle clustering mediated by α-synuclein.
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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
DOI：
10.1038/s41378-020-0147-1
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发表时间：
2020
影响因子：
7.9
通讯作者：
Diao J
中科院分区：
文献类型：
--
作者：
Cai B;Liu J;Zhao Y;Xu X;Bu B;Li D;Zhang L;Dong W;Ji B;Diao J
尽管大量研究表明α-突触核蛋白（α-Syn）蛋白在帕金森病、路易体痴呆和其他神经退行性疾病中起着核心作用，但该蛋白的生理功能仍然知之甚少。此外，尽管最近的报道表明，在Ca2+的影响下，α-Syn可以与突触囊泡相互作用，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Ca2+调节α-Syn介导的纳米级囊泡聚集的程度。研究结果表明，囊泡聚集不仅需要α-Syn与阴离子脂质囊泡结合，而且不同浓度的Ca2+对α-Syn诱导囊泡聚集的影响也不同。特别是，低浓度的Ca2+通过阻断脂质膜与α-Syn的N端之间的静电相互作用来抑制囊泡聚集，而高浓度的Ca2+促进囊泡聚集，可能是由于Ca2+与带负电荷的脂质之间的静电相互作用而独立于α-Syn。综上所述，我们的研究结果为α-Syn的生理功能以及Ca2+如何调节α-Syn介导的囊泡聚集提供了重要的见解。钙在α -突触核蛋白诱导的突触囊泡（神经元中储存着突触释放的各种神经递质）聚集中起着关键作用，不同钙浓度对这种聚集的影响不同。α -突触核蛋白是帕金森病和其他神经退行性疾病发展的关键因素：它已被证明在钙的影响下与突触囊泡相互作用，但其生理功能尚不清楚。美国辛辛那提大学医学院的赵佳杰及其同事利用单囊泡成像技术研究了钙如何调节α -突触核蛋白介导的囊泡聚集。他们发现，高钙浓度促进了囊泡的聚集而不依赖于α -突触核蛋白，但低钙浓度以α -突触核蛋白依赖的方式抑制囊泡的聚集。作者认为，他们的发现为α -突触核蛋白的生理功能提供了见解。
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. Calcium plays a critical role in the clustering of synaptic vesicles (which in a neuron store various neurotransmitters released at the synapse) induced by the protein alpha-synuclein, and different calcium concentrations exert different effects on such clustering. Alpha-synuclein is a key element in the development of Parkinson’s disease and other neurodegenerative conditions: it has been shown to interact with synaptic vesicles under the influence of calcium, but its physiological functions are poorly understood. Jiajie Diao of the University of Cincinnati College of Medicine, USA and colleagues used single-vesicle imaging to examine how calcium regulates vesicle clustering mediated by alpha-synuclein. They found that high calcium concentrations promoted vesicle clustering independent of alpha-synuclein, but low calcium concentrations inhibited vesicle clustering in an alpha-synuclein–dependent manner. The authors believe their findings provide insights into alpha-synuclein’s physiological function.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.5
作者：
Hess, Berk
通讯作者：
Hess, Berk
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG