Structure and regulation of synaptic architecture
突触结构的结构和调节
基本信息
- 批准号:8311045
- 负责人:
- 金额:$ 24.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAnimalsArchitectureAutomobile DrivingAwardBehavioralBindingBiochemicalBiochemical GeneticsBiologicalCell FractionationCell membraneCellsCellular StructuresComplexCuesCytoskeletonDefectDevelopmentDiseaseDrosophila genusEarly EndosomeEndocytosisEndosomesEukaryotaEventExhibitsFamily memberFluorescence MicroscopyFractionationFreeze SubstitutionFreezingGeneticGenotypeGrowthGrowth FactorHealthInstructionIntracellular MembranesLearningLipidsMediatingMembraneMembrane Protein TrafficMemoryMental RetardationMentorsMicrotubulesModelingMolecularMorphologyNeurodegenerative DisordersNeuromuscular JunctionNeuronsPathway interactionsPhasePhenotypePlayPopulationPositioning AttributePresynaptic TerminalsProcessPropertyProtein FamilyProteinsReagentRecyclingRegulationResolutionSH3 DomainsSamplingSeizuresSignal TransductionSorting - Cell MovementStructureSynapsesSynaptic VesiclesSynaptic plasticityTechnologyTemperatureTestingWiskott-Aldrich SyndromeWorkaddictionelectron tomographyflyin vivointerestloss of functionmutantnervous system disorderneuropsychiatryneurotransmitter releasenexinnovelpolymerizationpressurepresynapticreceptorreceptor internalizationresearch studyresponsesegregationsynaptic functionthree dimensional structurethree-dimensional modelingtrafficking
项目摘要
Structural plasticity contributes to long-lasting alterations in neuronal function during development, as well as
in learning and memory, and occurs in response to environmental and activity-dependent signaling
cascades. The receptors that transduce these synaptic growth signals are regulated by endocytic recycling,
but we do not understand what internal compartments they signal from, what special properties of those
compartments enable signaling to occur, and ultimately how the membrane traffic machinery itself can be
regulated to control synaptic growth. The intersection of signaling and membrane traffic is particularly
intriguing in the presynaptic compartment of neurons, because synapses are highly specialized for both
exocytic and endocytic traffic of synaptic vesicles in response to activity. Signaling receptor internalization
and the synaptic vesicle cycle use a highly overlapping set of trafficking machinery, but little is understood
about cross-talk between these processes and how activity-dependent modes of regulation of trafficking
machinery might be used to control signal transduction.
This proposal uses a combination of biochemical, genetic, and cell biological approaches in the Drosophila
larval neuromuscular junction (NMJ) to unravel the molecular mechanisms by which conserved membraneremodeling
proteins respond to extrinsic and intrinsic cues to modify signal transduction, leading to changes
in synaptic architecture. The aims of this proposal are (1) to characterize the biochemical activities and
interactions of lipid-deforming proteins that control receptor traffic at early endosomes and to evaluate how
these proteins work together in vivo; and (2) to obtain 3-dimenslonal high-resolution ultrastructures of
presynaptic endosomes at the NMJ, and to determine their relationship to other cellular structures in wildtype
and mutant animals. These receptor trafficking events are implicated in neuronal diseases ranging from
mental retardation to neurodegenerative disease and addiction, underlining the health importance of
understanding how signal transduction is modulated by intracellular membrane traffic in neurons.
结构可塑性有助于神经元功能在发育过程中的长期改变,以及
在学习和记忆中,并响应于环境和活动依赖性信号而发生
瀑布传递这些突触生长信号的受体受内吞再循环的调节,
但我们不知道它们是从什么内部隔间发出信号的,
隔间使信号发生,并最终如何膜交通机械本身可以
调节以控制突触生长。信号和膜交通的交叉点特别重要,
在神经元的突触前区室中很有趣,因为突触是高度专门化的
突触囊泡对活动的反应的胞吐和胞吞运输。信号受体内化
和突触囊泡周期使用一套高度重叠的运输机制,但人们对此知之甚少。
关于这些过程之间的相互作用以及依赖于活动的贩运管制模式
机器可能被用来控制信号转导。
该建议在果蝇中使用生物化学,遗传学和细胞生物学方法的组合
幼虫神经肌肉接头(NMJ),以解开保守的膜重塑的分子机制,
蛋白质对外在和内在的信号作出反应,改变信号转导,
在突触结构中。该提案的目的是(1)表征生物化学活性,
脂质变形蛋白的相互作用,控制受体交通在早期内涵体,并评估如何
这些蛋白质在体内一起工作;和(2)获得三维高分辨率的超微结构,
突触前核内体在NMJ,并确定其与其他细胞结构的关系,在野生型
和变异动物这些受体运输事件与神经元疾病有关,
精神发育迟缓、神经退行性疾病和成瘾,强调了健康的重要性
了解信号转导是如何被神经元细胞内的细胞膜运输所调节的。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck.
- DOI:10.1091/mbc.e13-05-0271
- 发表时间:2013-08
- 期刊:
- 影响因子:3.3
- 作者:Becalska AN;Kelley CF;Berciu C;Stanishneva-Konovalova TB;Fu X;Wang S;Sokolova OS;Nicastro D;Rodal AA
- 通讯作者:Rodal AA
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Avital Adah Rodal其他文献
Avital Adah Rodal的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Avital Adah Rodal', 18)}}的其他基金
Diversity Supplement (Monica Quinones-Frias): Roles of Recycling Endosomes in Neuronal Extracellular Vesicle Cargo Traffic
多样性补充剂(Monica Quinones-Frias):回收内体在神经元细胞外囊泡货物运输中的作用
- 批准号:
10782371 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Abberior 3D-STED microscope for super-resolution imaging
用于超分辨率成像的 Abberior 3D-STED 显微镜
- 批准号:
10630881 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Organization and Function of the Periactive Zone
周围活动区的组织和功能
- 批准号:
10600083 - 财政年份:2020
- 资助金额:
$ 24.04万 - 项目类别:
Organization and function of the periactive zone
周围活动区的组织和功能
- 批准号:
10381522 - 财政年份:2020
- 资助金额:
$ 24.04万 - 项目类别:
Mechanisms and regulation of extracellular vesicle traffic in the nervous system
神经系统细胞外囊泡运输的机制和调节
- 批准号:
10063578 - 财政年份:2017
- 资助金额:
$ 24.04万 - 项目类别:
Mechanisms and regulation of extracellular vesicle traffic in the nervous system
神经系统细胞外囊泡运输的机制和调节
- 批准号:
10308698 - 财政年份:2017
- 资助金额:
$ 24.04万 - 项目类别:
Roles of Recycling Endosomes in Neuronal Extracellular Vesicle Cargo Traffic
回收内体在神经元细胞外囊泡货物运输中的作用
- 批准号:
10584339 - 财政年份:2017
- 资助金额:
$ 24.04万 - 项目类别:
Activity-dependent regulation of membrane traffic and growth signaling in neurons
神经元膜交通和生长信号的活动依赖性调节
- 批准号:
8354138 - 财政年份:2012
- 资助金额:
$ 24.04万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 24.04万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 24.04万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 24.04万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 24.04万 - 项目类别:
Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
- 批准号:
23KK0126 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 24.04万 - 项目类别:
Training Grant