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DOI10.1073/pnas.2024029118
Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals
Radhakrishnan A.; Li X.; Grushin K.; Krishnakumar S.S.; Liu J.; Rothman J.E.
发表日期2021
ISSN00278424
卷号118期号:5
英文摘要Controlled release of neurotransmitters stored in synaptic vesicles (SVs) is a fundamental process that is central to all information processing in the brain. This relies on tight coupling of the SV fusion to action potential-evoked presynaptic Ca2+ influx. This Ca2+-evoked release occurs from a readily releasable pool (RRP) of SVs docked to the plasma membrane (PM). The protein components involved in initial SV docking/tethering and the subsequent priming reactions which make the SV release ready are known. Yet, the supramolecular architecture and sequence of molecular events underlying SV release are unclear. Here, we use cryoelectron tomography analysis in cultured hippocampal neurons to delineate the arrangement of the exocytosis machinery under docked SVs. Under native conditions, we find that vesicles are initially “tethered” to the PM by a variable number of protein densities (∼10 to 20 nm long) with no discernible organization. In contrast, we observe exactly six protein masses, each likely consisting of a single SNAREpin with its bound Synaptotagmins and Complexin, arranged symmetrically connecting the “primed” vesicles to the PM. Our data indicate that the fusion machinery is likely organized into a highly cooperative framework during the priming process which enables rapid SV fusion and neurotransmitter release following Ca2+ influx. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Cryoelecton tomography; SNARE protein; Synaptic vesicles; Vesicle priming
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180823
作者单位Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, United States; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520, United States; Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT 06520, United States
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Radhakrishnan A.,Li X.,Grushin K.,et al. Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals[J],2021,118(5).
APA Radhakrishnan A.,Li X.,Grushin K.,Krishnakumar S.S.,Liu J.,&Rothman J.E..(2021).Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA Radhakrishnan A.,et al."Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).
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