The role of a novel viral-like signalling pathway in synaptic plasticity and neurological disorders
新型病毒样信号通路在突触可塑性和神经系统疾病中的作用
基本信息
- 批准号:10430205
- 负责人:
- 金额:$ 36.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-15 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:3&apos Untranslated RegionsActinsAddressAmino Acid SequenceAntibodiesBehaviorBindingBiological ModelsCapsidCellsCo-ImmunoprecipitationsCommunicationCytoskeletonDegenerative DisorderDevelopmentDown-RegulationDrosophila genusEncapsulatedEpilepsyExhibitsGenesGeneticGenomeGoalsGrantHomologous GeneHumanInfectious AgentLearningMammalsMediatingMemoryMessenger RNAMolecularMultivesicular BodyMuscleNervous system structureNeuromuscular DiseasesNeuromuscular JunctionNeuronal PlasticityNeuronsPathway interactionsPhysiologicalPlayPresynaptic TerminalsProteinsRNARNA InterferenceRNA immunoprecipitation sequencingReagentReportingResearchReticulumRetrotransposonRoleSchizophreniaSelfish GenesSignal PathwaySignal TransductionSpinocerebellar AtaxiasSynapsesSynaptic VesiclesSynaptic plasticitySystemTestingTranscriptTransfer RNATravelUncertaintyUrsidae FamilyViralViral GenomeVirusWNT Signaling PathwayWorkexperimental studyextracellular vesiclesflygag Gene Productshuman diseaseintercellular communicationknock-downnervous system disorderneuromuscularneuron developmentneurotransmissionnovelparticlepostsynapticpresynapticprotein functiontraffickingviral RNA
项目摘要
We have discovered a novel viral-like signaling pathway associated with extracellular vesicles (EV). We
found the Drosophila homolog of ARC (Actin-Regulated Cytoskeleton-associated protein) (darc1), is
present in EVs as both an mRNA and protein. ARC is a master regulator of synaptic plasticity in the nervous
system of mammals and is crucial for learning and memory. dArc1 bears a domain resembling
retroviral/retrotransposon Gag-like proteins that multimerizes into a capsid that packages viral RNA. Our
work shows dARC1 forms a capsid, associates with its own RNA, and then transports the darc1 transcript
across the synapse. The transfer of dArc1 is needed for activity-dependent plasticity at the fly
neuromuscular junction (NMJ). Besides dArc1, it is unknown whether other genes are in this viral-like
pathway. We address this uncertainty in Aim 1. Here we describe our plan to identify other Gag-like
proteins in EVs, and we have already found another Gag protein enriched in EVs, that is encoded by the
retrotransposon Copia. We have found that Copia transfers across the synaptic bouton. When copia is
knocked down at the NMJ this strikingly leads to increased plasticity. This is the opposite of darc1, where
we reported a decrease in plasticity. In Aim 2 we focus on what cargoes are co-transferring with dArc1 and
Copia. We have identified through co-immunoprecipitation, mRNAs and proteins that associate with dArc1
and Copia. As to how the transfer of Arc occurs, we have found that the dArc1 3’untranslated region (UTR)
is necessary and sufficient for the transfer of dArc1 across synaptic boutons. We are now testing if the
dArc1 3’UTR directs the loading of dArc1 into EVs. As well, we propose experiments to understand how
darc1 and copia mediate synaptic plasticity. We have co-immunoprecipitated dArc1 and Copia to identify
potential interactors, and we will take a candidate approach to find genetic interactors. In preliminary work
we found that dArc1 is needed for proper WNT pathway signaling at the NMJ. Additionally, we observe
that Copia and dArc1 bind to some of the same proteins and mRNAs, suggesting that they may be
antagonistic to each other, thus potentially explaining their seemingly opposite roles in mediating plasticity.
Through this grant we will expand our understanding of EV trafficking and synaptic plasticity, while
describing a novel physiological function of a retrotransposon in neuronal communication.
我们发现了一种新的与细胞外囊泡(EV)相关的病毒样信号通路。我们
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 }}
Travis Thomson其他文献
Travis Thomson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('Travis Thomson', 18)}}的其他基金
The Role of a Novel Viral-Like Signaling Pathway in Synaptic Plasticity and Neurological Disorders
新型病毒样信号通路在突触可塑性和神经系统疾病中的作用
- 批准号:
10640952 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
The role of a novel viral-like signalling pathway in synaptic plasticity and neurological disorders
新型病毒样信号通路在突触可塑性和神经系统疾病中的作用
- 批准号:
10187668 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
The role of a novel viral-like signalling pathway in synaptic plasticity and neurological disorders
新型病毒样信号通路在突触可塑性和神经系统疾病中的作用
- 批准号:
9802983 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
相似海外基金
Impact of alternative polyadenylation of 3'-untranslated regions in the PI3K/AKT cascade on microRNA
PI3K/AKT 级联中 3-非翻译区的替代多聚腺苷酸化对 microRNA 的影响
- 批准号:
573541-2022 - 财政年份:2022
- 资助金额:
$ 36.64万 - 项目类别:
University Undergraduate Student Research Awards
How do untranslated regions of cannabinoid receptor type 1 mRNA determine receptor subcellular localisation and function?
1 型大麻素受体 mRNA 的非翻译区如何决定受体亚细胞定位和功能?
- 批准号:
2744317 - 财政年份:2022
- 资助金额:
$ 36.64万 - 项目类别:
Studentship
MICA:Synthetic untranslated regions for direct delivery of therapeutic mRNAs
MICA:用于直接递送治疗性 mRNA 的合成非翻译区
- 批准号:
MR/V010948/1 - 财政年份:2021
- 资助金额:
$ 36.64万 - 项目类别:
Research Grant
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10019570 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10223370 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10455108 - 财政年份:2019
- 资助金额:
$ 36.64万 - 项目类别:
Synergistic microRNA-binding sites, and 3' untranslated regions: a dialogue of silence
协同的 microRNA 结合位点和 3 非翻译区:沉默的对话
- 批准号:
255762 - 财政年份:2012
- 资助金额:
$ 36.64万 - 项目类别:
Operating Grants
Analysis of long untranslated regions in Nipah virus genome
尼帕病毒基因组长非翻译区分析
- 批准号:
20790351 - 财政年份:2008
- 资助金额:
$ 36.64万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Search for mRNA elements involved in the compatibility between 5' untranslated regions and coding regions in chloroplast translation
寻找参与叶绿体翻译中 5 非翻译区和编码区之间兼容性的 mRNA 元件
- 批准号:
19370021 - 财政年份:2007
- 资助金额:
$ 36.64万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Post-transcriptional Regulation of PPAR-g Expression by 5'-Untranslated Regions
5-非翻译区对 PPAR-g 表达的转录后调控
- 批准号:
7131841 - 财政年份:2006
- 资助金额:
$ 36.64万 - 项目类别: