Genetics of New Synaptic Components and Their Functions
新突触成分的遗传学及其功能
基本信息
- 批准号:9271262
- 负责人:
- 金额:$ 56.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-04-01 至 2018-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAnatomyAreaBindingBiochemicalBiochemical GeneticsBiological ModelsBrainCell membraneCellsCollagen Type IVComplexDataDendritic SpinesDevelopmentDietDiseaseDrosophila genomeDrosophila genusEatingElementsEmbryoFastingGeneticGlutamate ReceptorGrowthGrowth ConesHippocampus (Brain)Hypothalamic structureIn VitroInvertebratesMammalsMediatingMediator of activation proteinMembraneMembrane Protein TrafficMethodsMolecularMonomeric GTP-Binding ProteinsMorphologyMutationNeuritesNeuromuscular JunctionNeuronsPathway interactionsPatternPlasticizersPostsynaptic MembranePresynaptic TerminalsProcessProteinsRecruitment ActivityRegulationReticulumRoleShapesSideSignaling MoleculeSliceSwellingSynapsesSynaptic VesiclesSynaptic plasticityTestingTimeTransmembrane TransportTransport VesiclesVertebral columnenvironmental changeflygenetic approachin vivomutantnovelpostsynapticpresynapticpreventpublic health relevanceresponsesynaptogenesistraffickingvoltage
项目摘要
DESCRIPTION (provided by applicant): This proposal focuses on two types of change in synapse morphology: expansion of postsynaptic membranes and formation of presynaptic boutons. Anatomical specializations are a hallmark of synapses. On the postsynaptic side, anatomical specializations include dendritic spines and membrane folds. On the presynaptic side, an enlargement of the neurite to form a rounded presynaptic bouton or en passant swelling is a nearly universal feature of synapses. Aim 1 of this proposal tests a specific hypothesis for how activity can regulate anatomical changes at the postsynapse in the fly neuromuscular junction and in mammalian dendritic spines. In particular, it seeks to elucidate the role of Ral as
a mediator of activity-dependent anatomical plasticity. We have uncovered a novel pathway for synaptic plasticity in which the small GTPase Ral, by activating the exocyst complex, serves a central role in transducing Ca2+ influx from glutamate receptors into enhanced transport of membrane to the postsynaptic region. In consequence, the membrane area of the postsynaptic specialization at the fly neuromuscular junction (NMJ) expands in an activity-dependent manner. This proposal asks what patterns of synaptic activity are necessary to recruit the exocyst and how Ral comes to be localized to postsynaptic membranes. It goes on to investigate the significance of Ral for the formation of dendritic spines in the mammalian CNS. Aim 2 uses Drosophila as a model system in which to uncover the machinery that allows synaptic boutons to form. The maturation of presynaptic terminals from growth cones to synaptic boutons is a critical late step in synaptogenesis but poorly understood. Neither the cytoskeletal elements that underlie the shape change nor signaling molecules that trigger it are known. In a previous mutant screen in Drosophila we discovered that mutations in 2-3 arrest synaptogenesis after initial synapse formation and prevent the formation of synaptic boutons at the fly NMJ. We propose to pursue the process of bouton formation in greater detail by a combination of biochemical and genetic approaches to uncover additional players in the formation of this poorly understood aspect of synaptic anatomy. Therefore, in Aim 2A we will use biochemical methods to identify binding partners for 2-3 and determine if they are required for bouton formation. In Aim 2B we will uncover additional players in bouton formation through a mutant screen of the Drosophila genome at the embryonic NMJ.
描述(由申请人提供):本提案侧重于突触形态的两种类型的变化:突触后膜的扩张和突触前钮扣的形成。解剖学上的特化是突触的标志。在突触后侧,解剖特化包括树突棘和膜褶皱。在突触前侧,神经突的扩大形成一个圆形的突触前钮扣或短暂的肿胀几乎是突触的普遍特征。本提案的目的1测试了一个特定的假设,即活动如何调节果蝇神经肌肉连接处和哺乳动物树突棘突触后的解剖变化。特别是,它试图阐明Ral的作用
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction.
- DOI:10.1523/jneurosci.0164-08.2008
- 发表时间:2008-10-22
- 期刊:
- 影响因子:0
- 作者:Miech C;Pauer HU;He X;Schwarz TL
- 通讯作者:Schwarz TL
Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions.
- DOI:10.1038/nn.2417
- 发表时间:2009-11
- 期刊:
- 影响因子:25
- 作者:Kurshan PT;Oztan A;Schwarz TL
- 通讯作者:Schwarz TL
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Thomas L. Schwarz其他文献
Discovery of small molecule pathway regulators by image 2 profile matching
通过图像 2 配置文件匹配发现小分子途径调节剂
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
M. Rohban;Ashley M. Fuller;Ceryl Tan;Jonathan T. Goldstein;Deepsing Syangtan;Madhura P. Nijsure;M. Rigby;Joshua R. Sacher;S. M. Corsello;Grace B. Peppler;Marta;Bogaczynska;Gabrielle E Ciotti;Ann DeVine;M. Doan;Jennifer P. Gale;Rik Derynck;T. Turbyville;J. Boerckel;Shantanu Singh;L. Kiessling;Thomas L. Schwarz;X. Varelas;Ran Kafri;T. S. Eisinger;Anne E Carpenter - 通讯作者:
Anne E Carpenter
Thomas L. Schwarz的其他文献
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{{ truncateString('Thomas L. Schwarz', 18)}}的其他基金
Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
- 批准号:
10891859 - 财政年份:2023
- 资助金额:
$ 56.29万 - 项目类别:
Genetic dissection of lateral septal circuitry that controls stress-induced persistent anxiety states
控制压力引起的持续焦虑状态的外侧间隔电路的基因解剖
- 批准号:
10542797 - 财政年份:2019
- 资助金额:
$ 56.29万 - 项目类别:
Genetic dissection of lateral septal circuitry that controls stress-induced persistent anxiety states
控制压力引起的持续焦虑状态的外侧间隔电路的基因解剖
- 批准号:
10748497 - 财政年份:2019
- 资助金额:
$ 56.29万 - 项目类别:
Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
- 批准号:
10248433 - 财政年份:2019
- 资助金额:
$ 56.29万 - 项目类别:
Kinetochore Protein Functions in Synaptogenesis
动粒蛋白在突触发生中的功能
- 批准号:
10017352 - 财政年份:2019
- 资助金额:
$ 56.29万 - 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
- 批准号:
10210451 - 财政年份:2018
- 资助金额:
$ 56.29万 - 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
- 批准号:
9921501 - 财政年份:2018
- 资助金额:
$ 56.29万 - 项目类别:
Axonal Transport of mRNA for Mitochondrial Proteins
线粒体蛋白 mRNA 的轴突运输
- 批准号:
10430133 - 财政年份:2018
- 资助金额:
$ 56.29万 - 项目类别:
2016 Cell Biology of the Neuron Gordon Research Conference and Gordon Research Seminar
2016年神经元细胞生物学戈登研究会议暨戈登研究研讨会
- 批准号:
9193674 - 财政年份:2016
- 资助金额:
$ 56.29万 - 项目类别:
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