LKB1 function in axon development through regulation of mitochondrial trafficking
LKB1 通过调节线粒体运输在轴突发育中发挥作用
基本信息
- 批准号:8397082
- 负责人:
- 金额:$ 4.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-01 至 2015-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAxonAxonal TransportBiochemicalBiological AssayCell DeathCellsCo-ImmunoprecipitationsDefectDevelopmentDynein ATPaseElectroporationEndosomesGeneticGoalsHeartHuntington DiseaseIn VitroKinesinKnock-outKnowledgeLeadLinkMaintenanceMediatingMicroscopyMitochondriaMolecularNervous system structureNeurodegenerative DisordersNeuronsParkinson DiseasePathway interactionsPhenotypePhosphorylationPhosphotransferasesPlayPreparationPresynaptic TerminalsPropertyProteinsRegulationResearchSTK11 geneSurfaceSynapsesTestingTimeVenusVesicleWorkanterograde transportaxon growthcell motilityin uteroin vivoinsightloss of functionneuron developmentpolarized cellpresynapticresearch studyretrograde transportsyntaphilintime usetrafficking
项目摘要
DESCRIPTION (provided by applicant): The development and maintenance of polarity is paramount to neuronal development and function. The loss of this cell state is realized in many neurodegenerative diseases and ultimately leads to cell death. This project will lead to a greater understanding of the mechanisms responsible for polarization and its maintenance. The goal of this project is to characterize the contribution that the recently discovered LKB1 kinase pathway plays in axon growth and branching through polarized transport of cargo. Specific Aim 1 will provide the necessary framework for understanding how LKB1 and NUAK1/2 affect the transport of mitochondria in the axon. Specific Aim 2 will characterize the mechanism by which transport is regulated by determining the downstream components of the kinase pathway. The interaction between LKB1/NUAK and the mitochondrial anchor protein syntaphilin will be the main focus of this aim. Specific Aim 3 will then attempt to link mitochondrial transport in the axon to proper axon branching and projection within layer 2/3 neurons of the cortex. This research will provide important new knowledge that will be useful in understanding the basic mechanisms at work in many neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's.
PUBLIC HEALTH RELEVANCE: Neuron polarization is required for proper neuron function. Disruption of polarization and the mechanisms that underlie its maintenance are known to be major factors in many neurodegenerative diseases including ALS, Alzheimer's, Huntington's and Parkinson's.
描述(由申请人提供):极性的发展和维持对神经元的发育和功能至关重要。这种细胞状态的丧失在许多神经退行性疾病中实现,并最终导致细胞死亡。该项目将使人们更好地了解导致两极分化及其维持的机制。该项目的目标是表征最近发现的LKB 1激酶途径通过极化运输货物在轴突生长和分支中的贡献。具体目标1将为理解LKB 1和NUAK 1/2如何影响轴突中线粒体的运输提供必要的框架。具体目标2将通过确定激酶途径的下游组分来表征调节转运的机制。LKB 1/NUAK和线粒体锚蛋白syntaphilin之间的相互作用将是这一目标的主要焦点。然后,特定目标3将尝试将轴突中的线粒体转运与皮质的第2/3层神经元内的适当轴突分支和投射联系起来。这项研究将提供重要的新知识,有助于理解许多神经退行性疾病(包括阿尔茨海默氏症、亨廷顿氏症和帕金森氏症)的基本机制。
公共卫生相关性:神经元极化是正常神经元功能所必需的。已知极化的破坏及其维持的基础机制是许多神经退行性疾病(包括ALS、阿尔茨海默病、亨廷顿病和帕金森病)的主要因素。
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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Tommy L Lewis其他文献
Tommy L Lewis的其他文献
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{{ truncateString('Tommy L Lewis', 18)}}的其他基金
Molecular and cellular mechanisms regulating mitochondrial subpopulation dynamics and function in vivo
体内调节线粒体亚群动态和功能的分子和细胞机制
- 批准号:
10214639 - 财政年份:2020
- 资助金额:
$ 4.92万 - 项目类别:
Molecular and cellular mechanisms regulating mitochondrial subpopulation dynamics and function in vivo
体内调节线粒体亚群动态和功能的分子和细胞机制
- 批准号:
10404686 - 财政年份:2020
- 资助金额:
$ 4.92万 - 项目类别:
Molecular and cellular mechanisms regulating mitochondrial subpopulation dynamics and function in vivo
体内调节线粒体亚群动态和功能的分子和细胞机制
- 批准号:
10027150 - 财政年份:2020
- 资助金额:
$ 4.92万 - 项目类别:
Molecular and cellular mechanisms regulating mitochondrial subpopulation dynamics and function in vivo
体内调节线粒体亚群动态和功能的分子和细胞机制
- 批准号:
10620309 - 财政年份:2020
- 资助金额:
$ 4.92万 - 项目类别:
In vivo investigation of mitochondrial dynamics in the mouse brain
小鼠大脑线粒体动力学的体内研究
- 批准号:
9104224 - 财政年份:2015
- 资助金额:
$ 4.92万 - 项目类别:
In vivo investigation of mitochondrial dynamics in the mouse brain
小鼠大脑线粒体动力学的体内研究
- 批准号:
8869236 - 财政年份:2015
- 资助金额:
$ 4.92万 - 项目类别:
LKB1 function in axon development through regulation of mitochondrial trafficking
LKB1 通过调节线粒体运输在轴突发育中发挥作用
- 批准号:
8786967 - 财政年份:2012
- 资助金额:
$ 4.92万 - 项目类别:
LKB1 function in axon development through regulation of mitochondrial trafficking
LKB1 通过调节线粒体运输在轴突发育中发挥作用
- 批准号:
8694114 - 财政年份:2012
- 资助金额:
$ 4.92万 - 项目类别:
LKB1 function in axon development through regulation of mitochondrial trafficking
LKB1 通过调节线粒体运输在轴突发育中发挥作用
- 批准号:
8502190 - 财政年份:2012
- 资助金额:
$ 4.92万 - 项目类别: