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：
Avital Adah Rodal
金额：
$ 24.04万
依托单位：
BRANDEIS UNIVERSITY
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：
https://reporter.nih.gov/project-details/8311045
关键词：
Actins Animals Architecture Automobile Driving Award Behavioral Binding Biochemical Biochemical Genetics Biological Cell Fractionation Cell membrane Cells Cellular Structures Complex Cues Cytoskeleton Defect Development Disease Drosophila genus Early Endosome Endocytosis Endosomes Eukaryota Event Exhibits Family member Fluorescence Microscopy Fractionation Freeze Substitution Freezing Genetic Genotype Growth Growth Factor Health Instruction Intracellular Membranes Learning Lipids Mediating Membrane Membrane Protein Traffic Memory Mental Retardation Mentors Microtubules Modeling Molecular Morphology Neurodegenerative Disorders Neuromuscular Junction Neurons Pathway interactions Phase Phenotype Play Population Positioning Attribute Presynaptic Terminals Process Property Protein Family Proteins Reagent Recycling Regulation Resolution SH3 Domains Sampling Seizures Signal Transduction Sorting - Cell Movement Structure Synapses Synaptic Vesicles Synaptic plasticity Technology Temperature Testing Wiskott-Aldrich Syndrome Work addiction electron tomography fly in vivo interest loss of function mutant nervous system disorder neuropsychiatry neurotransmitter release nexin novel polymerization pressure presynaptic receptor receptor internalization research study response segregation synaptic function three dimensional structure three-dimensional modeling trafficking

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.

结构可塑性有助于发育过程中神经元功能的长期变化，以及在学习和记忆中，并响应于环境和活动依赖性信号传导级联。转导这些突触生长信号的受体受到内吞回收的调节，但是我们不明白他们从中发出的内部隔间，这些内部隔间的特殊属性隔室使信令能够发生，并最终如何可以进行膜交通机械本身受监管以控制突触生长。信号和膜流量的交集特别是在神经元的突触前室中引人入胜，因为突触高度专业化突触囊泡的外生和内吞流量响应活性。信号受体内在化突触囊泡周期使用了一组高度重叠的贩运机械，但几乎没有理解关于这些过程之间的串扰以及依赖活动的运输模式机械可用于控制信号转导。该提案结合了果蝇中的生化，遗传和细胞生物学方法幼虫神经肌肉连接（NMJ），以揭示保守的膜模型的分子机制蛋白质对外在和内在提示做出反应以修饰信号转导，导致变化在突触体系结构中。该提案的目的是（1）表征生化活动和在早期内体中控制受体流量的脂质变形蛋白的相互作用，并评估如何这些蛋白质在体内共同起作用；（2）获得3-二维拉尔的高分辨率超微结构 NMJ处突触前内体，并确定它们与野生型中其他细胞结构的关系和突变动物。这些受体运输事件与神经元疾病有关对神经退行性疾病和成瘾的智力降低，强调了健康的重要性了解信号转导如何通过神经元的细胞内膜流量调节。

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：
Molecular biology of the cell
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