Exploring how cells generate and release distinct subpopulations of dense-core vesicles
探索细胞如何产生和释放不同的致密核心囊泡亚群
基本信息
- 批准号:10679873
- 负责人:
- 金额:$ 23.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-15 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAfferent NeuronsBehaviorBehavior ControlBehavior DisordersBeta CellBiogenesisBiogenic AminesBiologicalBiological ModelsCaenorhabditis elegansCalciumCell LineCellsCellular biologyCharacteristicsDataDefectDense Core VesicleDiseaseDopamineElectron MicroscopyEndocrineEndosomesFamilyFunctional disorderFutureGenerationsHeterogeneityIndividualInsulinInvestigationKnowledgeLipidsMental disordersMetabolic DiseasesMetabolismMolecularMood DisordersNematodaNerve Growth FactorsNeurologicNeuromodulatorNeuronsNeuropeptidesNorepinephrineOrganellesPathway interactionsPatternPeptidesPhysiologicalPhysiologyPopulationProcessProtein IsoformsProteinsRattusRecyclingRoleSensorySignaling MoleculeSiteSortingStructure of beta Cell of isletSystemTestingVesiclecell typeexperimental studyinsightmembermonoaminenervous system disorderpeptide hormoneprotein complexrab GTP-Binding Proteinssegregationsensorsynaptotagminvesicular release
项目摘要
Project summary
When examined by electron microscopy, neurons can be seen to carry organelles that look like little black dots.
These black dots are called dense-core vesicles and they carry many important transmitters that act as
neuromodulators, including neuropeptides, nerve growth factors, and monoamines such as dopamine and
norepinephrine. Such dense-core vesicle cargos regulate a wide array of behaviors, and defects in such
cargos can contribute to numerous mood disorders and other neurological conditions. However, little is
understood about the cell biology of how dense-core vesicles are made, acquire cargos and mature, are
trafficked to release sites, and ultimately released. Thus, the little black dots in neurons are really a big black
box. Adding to the mysteries and complexity of these organelles, many neurons carry multiple dense-core
vesicle cargos in the same cell. Are these different cargos copackaged together in the same dense-core
vesicles or are they packaged separately in distinct vesicles? The answer to this question is surprisingly known
in only a few cases, and the general pattern of copackaging versus segregation of distinct cargos is unclear,
but is of key physiological relevance as it determines whether different dense-core vesicle cargos are
coreleased or can be released independently. Additionally, in cases where distinct dense-core vesicle
subpopulations are known to exist in the same cell, it is unclear how these distinct populations are generated
and how cargos are differentially sorted. To begin to address these gaps in understanding, here we aim to
establish two model systems for the study of distinct dense-core vesicle populations in the same cell: the ASI
sensory neuron in the nematode C. elegans and the rat pancreatic beta-cell line 832/13. Our preliminary data
show that members of a known dense-core vesicle biogenesis and maturation pathway, the Rab2/EARP
pathway, are required for one subpopulation of dense-core vesicles in both the ASI neuron and the 832/13 cell
line, but not for another subpopulation in the same cell. In Aim 1, we will further define the requirements for
members of the Rab2/EARP pathway in the biogenesis and maturation of distinct dense-core vesicle
subpopulations in the ASI neuron and 832/13 cells. Additionally, we will perform candidate screens in an
attempt to identify factors required for the Rab2/EARP-independent generation of dense-core vesicles in both
cell types. In Aim 2, we will test the hypothesis that different subpopulations of dense-core vesicles are marked
by different isoforms of the synaptotagmin family of calcium sensors. We will also determine whether these
synaptotagmins control the release of distinct dense-core vesicle subpopulations. In summary, this project will
identify the basic molecules required for the generation and release of distinct subpopulations of dense-core
vesicles in the same cell, and set the stage for more mechanistic investigations into how these processes
occur.
项目总结
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)
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Michael Ailion其他文献
Michael Ailion的其他文献
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{{ truncateString('Michael Ailion', 18)}}的其他基金
Signaling pathways that modulate neuronal activity
调节神经元活动的信号通路
- 批准号:
9884109 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Signaling pathways that modulate neuronal activity
调节神经元活动的信号通路
- 批准号:
10322413 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Signaling pathways that modulate neuronal activity
调节神经元活动的信号通路
- 批准号:
10524779 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Proteins important for dense-core vesicle function
对致密核心囊泡功能重要的蛋白质
- 批准号:
10337224 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
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