Dynamic Control of Local Synaptic-Membrane Protein Composition by the Dendritic Secretory Pathway
树突分泌途径动态控制局部突触膜蛋白组成
基本信息
- 批准号:9270091
- 负责人:
- 金额:$ 4.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-06-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AMPA ReceptorsAddressAlzheimer&aposs DiseaseAreaAutistic DisorderCell Adhesion MoleculesCell membraneCell surfaceCharacteristicsCognitionComplementDataDendritesDevelopmentDevelopmental Delay DisordersDiffusionDimensionsDiseaseEndoplasmic ReticulumFoundationsFutureGlutamate ReceptorGlutamatesGolgi ApparatusHuntington DiseaseImpaired cognitionIntegral Membrane ProteinIon ChannelKineticsLeadLearningLigandsLocationMediator of activation proteinMembraneMembrane ProteinsMemoryMicroscopyNeuronal PlasticityNeuronsNeurosciencesNeurotransmitter ReceptorOrganellesPathway interactionsPharmacologyPlasmaPlayProcessPropertyProtein BiosynthesisProteinsResolutionRoleSchizophreniaSignal TransductionSiteSpatial DistributionStimulusSurfaceSynapsesSynaptic MembranesSynaptic plasticitySystemTestingTranslatingTranslationsVariantaddictionautism spectrum disorderbasecognitive functionexperienceexperimental studymembrane synthesisneural patterningneuroligin 1neuronal cell bodyneuropsychiatric disorderprotein transportpublic health relevancereceptorresponsesmall moleculetargeted deliverytrafficking
项目摘要
DESCRIPTION (provided by applicant): During learning and memory formation, synaptic connections between neurons are selectively reorganized based on patterns of neural activity in a process called "synaptic plasticity". Underlying this phenomenon is the precise, regulated delivery of synaptic proteins, such as neurotransmitter receptors, adhesion molecules and ion channels that modify synaptic strength and cellular excitability in response to activity. Local translation has emerged as an important mechanism that facilitates protein delivery to dendritic locations long-distances from the neuronal soma. A diverse array of soluble and integral-membrane proteins are locally synthesized, including glutamate receptor subunits and neuroligins that are important for certain forms of synaptic plasticity. However, the delivery of integral-membrane proteins is complicated by the fact that they require not just the machinery for protein synthesis, but also trafficking through the entire complement of secretory organelles to reach the cell surface. Studies characterizing the dendritic secretory organelles have revealed that many of the post-endoplasmic reticulum (ER) organelles, such as Golgi Complex, are scarce within the dendrite and their functional significance unclear. Consequently, it is unknown whether locally translated proteins undergo delivery to nearby areas of the dendritic membrane, or if there are specific signals that control their delivery. This proposal addresses the hypothesis that the distribution of synaptic cargo within the dendritic early secretory pathway
spatially defines its delivery to the dendritic plasma membrane and that synaptic activity is a key
regulatory of this process. I will investigate thhis hypothesis by tracking synaptic proteins as they traffic from the dendritic ER (the site of local synthesis for membrane proteins) to the plasma membrane to determine the range and kinetics of their delivery. The results will reveal whether the secretory pathway exerts spatial and temporal control of trafficking in order to direct
cargo to specific dendritic locations, thus selectively modifying certain synapses. Overall, the findings will provide a foundation to understand the contribution of the secretory pathway to fundamental aspects of normal cognition, as well as how perturbed secretory trafficking may lead to cognitive dysfunction in a wide variety of diseases and disorders, including Alzheimer's disease, developmental delay, Huntington's disease, and autistic disorders.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Aaron Bowen其他文献
Aaron Bowen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('Aaron Bowen', 18)}}的其他基金
Dynamic Control of Local Synaptic-Membrane Protein Composition by the Dendritic Secretory Pathway
树突分泌途径动态控制局部突触膜蛋白组成
- 批准号:
9084272 - 财政年份:2015
- 资助金额:
$ 4.4万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 4.4万 - 项目类别:
Research Grant