Spatial and molecular determinants of fusion probability and timing
融合概率和时间的空间和分子决定因素
基本信息
- 批准号:10443756
- 负责人:
- 金额:$ 35.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAddressAffinityAntibodiesBackBinding SitesBiochemicalBungarotoxinsCalciumCalcium ChannelCalcium Channel BlockersCell membraneChemical SynapseCommunicationConsumptionCoupledCouplesDataDefectDiseaseDockingEgtazic AcidElectric StimulationElectron MicroscopyElectronsEventExocytosisFerritinFreezingGeneticGoalsGoldHippocampus (Brain)ImageIndividualKineticsLabelLiquid substanceLocationMapsMediatingMembraneMethodsModelingMolecularMolecular BiologyMusNeuronsNeurotransmittersNickelPathogenesisPhasePlayPresynaptic TerminalsProbabilityProcessProteinsPsyche structureRecyclingResearchResolutionRoleSNAP receptorSiteSynapsesSynaptic TransmissionSynaptic VesiclesTechniquesTestingTimeVAMP-2Vesiclechemical releaseexperimental studymillisecondmolecular modelingnanomagneticnanoparticlenanoscalenervous system disorderneurotransmissionneurotransmitter releasenovelparticlepredictive modelingpressurerecruitsensorsynaptotagmin Itraffickingvesicular SNARE proteins
项目摘要
At chemical synapses, neurons communicate each other through release of neurotransmitters.
Synaptic transmission occurs in two kinetically distinct phases. Within milliseconds of an action potential,
synaptic vesicles fuse with the plasma membrane synchronously across multiple synapses. Following
synchronous fusion, synaptic vesicles continue to fuse with the plasma membrane over tens to hundreds of
milliseconds. This phase of neurotransmission is called asynchronous release, and it becomes more apparent
in pathophysiological conditions. Despite extensive research over the last 50 years, the nano-scale
organization of synaptic vesicle fusion sites is poorly understood. Where do synchronous and asynchronous
fusions take place within an active zone? Are fusion sites determined by the locations of calcium channels?
Which calcium sensors are responsible for asynchronous fusion? Is there a separate pool of vesicles for
asynchronous fusion? Or are the same pool of vesicles consumed for both phases? To address these
questions, we have developed zap-and-freeze electron microscopy to follow membrane dynamics millisecond-
by-millisecond. This technique couples electrical stimulation of neurons with high-pressure freezing to capture
rapid membrane trafficking events at mammalian central synapses with unprecedented spatial (1 nm) and
temporal (1 ms) resolution. Using this approach in combinations with advanced genetics, molecular biology,
and biochemical techniques, we will determine how fusion sites are organized at mammalian central synapses.
Defects in synaptic transmission play a causal role in neurological disorders. The proposed research aims to
understand the molecular mechanisms underlying synaptic transmission with the ultimate goal of
understanding the pathogenesis of these diseases.
在化学突触中,神经元通过释放神经递质相互交流。
突触传递发生在两个动力学上不同的阶段。在动作电位的几毫秒内,
突触囊泡在多个突触中与质膜同步融合。以下
同步融合,突触囊泡继续与质膜融合数十至数百年,
毫秒神经传递的这一阶段被称为异步释放,它变得更加明显
在病理生理条件下。尽管在过去的50年里进行了广泛的研究,
对突触囊泡融合位点的组织了解甚少。同步和异步
核聚变会发生在活跃区吗融合部位是由钙通道的位置决定的吗?
哪些钙传感器负责异步融合?是否有一个单独的囊泡池,
异步聚变?还是两个阶段消耗的囊泡相同?解决这些
问题,我们已经开发了zap和冻结电子显微镜跟踪膜动力学毫秒-
以毫秒为单位这项技术将神经元的电刺激与高压冷冻结合起来,
在哺乳动物中央突触处的快速膜运输事件具有前所未有的空间(1 nm)和
时间(1 ms)分辨率。将这种方法与先进的遗传学,分子生物学,
和生物化学技术,我们将确定融合位点是如何组织在哺乳动物中央突触。
突触传递的缺陷在神经系统疾病中起着因果作用。拟议的研究旨在
了解突触传递的分子机制,最终目标是
了解这些疾病的发病机制。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transient docking of synaptic vesicles: Implications and mechanisms.
- DOI:10.1016/j.conb.2022.102535
- 发表时间:2022-06
- 期刊:
- 影响因子:5.7
- 作者:
- 通讯作者:
Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.
Dynamin 1xA 通过其剪接的长 C 末端与 Endophilin A1 相互作用,实现超快内吞作用。
- DOI:10.1101/2023.09.21.558797
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Imoto,Yuuta;Xue,Jing;Luo,Lin;Raychaudhuri,Sumana;Itoh,Kie;Ma,Ye;Craft,GeorgeE;Kwan,AnnH;Mackay,JoelP;Ha,Taekjip;Watanabe,Shigeki;Robinson,PhillipJ
- 通讯作者:Robinson,PhillipJ
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Shigeki Watanabe其他文献
Shigeki Watanabe的其他文献
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{{ truncateString('Shigeki Watanabe', 18)}}的其他基金
Spatial and molecular determinants of fusion probability and timing
融合概率和时间的空间和分子决定因素
- 批准号:
10226174 - 财政年份:2018
- 资助金额:
$ 35.82万 - 项目类别:
Spatial and molecular determinants of fusion probability and timing
融合概率和时间的空间和分子决定因素
- 批准号:
9977278 - 财政年份:2018
- 资助金额:
$ 35.82万 - 项目类别:
Spatial and molecular determinants of fusion probability and timing
融合概率和时间的空间和分子决定因素
- 批准号:
9789391 - 财政年份:2018
- 资助金额:
$ 35.82万 - 项目类别:
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