Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
基本信息
- 批准号:10318573
- 负责人:
- 金额:$ 43.28万
- 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:2019-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdultAffectAttenuatedAxonBiochemicalBiochemistryCaliberCarbonCell physiologyCellsCellular StructuresCoupledCouplesCouplingCuesCytoplasmDevelopmentDistalEndosomesEnsureEnvironmentEnzymesGoalsGrowthGrowth ConesHomeostasisImageInjuryKnowledgeLengthLifeLinkLipidsMaintenanceMeasuresMediatingMessenger RNAModificationMonitorMonomeric GTP-Binding ProteinsMorphologyMusNGFR ProteinNatural regenerationNerve Growth FactorsNeuronsPharmacologyPhosphorylationPresynaptic TerminalsProcessProtein BiosynthesisProtein GeranylgeranylationProtein InhibitionProtein IsoprenylationProteinsRNARegulationRoleSignal TransductionSympathetic GangliaTestingTissuesTransferaseTranslationsaxon growthexperimental studygeranylgeranylationimprovedin vivomouse geneticsmutantnerve repairnerve supplyneurotrophic factornovel therapeuticspolarized cellprenylprenylationprotein expressionprotein functionrecruitrepairedresponsespatiotemporaltrafficking
项目摘要
Axons continuously respond to external signals in their environment as they grow and
navigate toward their target tissues during development, and for maintenance and repair
in adult life. mRNA localization and local protein synthesis is a conserved mechanism that
allows for rapid and axon-autonomous responses to external trophic and guidance cues.
Despite growing appreciation for the functions of axonal protein synthesis, a major gap in
our knowledge is in understanding how the nascent proteins are further processed and
localized in axons to generate fully functional proteins. Our preliminary results suggest
that a neurotrophic factor (Nerve Growth Factor) acutely regulates local protein synthesis
and lipidation (prenylation) of newly-made proteins in axons. It has been assumed that
protein prenylation is a constitutive mechanism that occurs throughout the cytoplasm and
is permissive for cellular functions. In striking contrast, we find that, in neurons, prenylation
is under exquisite spatio-temporal control by extrinsic signals. The goal of this application
is to define whether coupled axonal protein synthesis and prenylation serves as a
regulatory mechanism to localize and enrich proteins in axonal compartments to ensure
dynamic and spatial responses to extrinsic growth-promoting cues. We will use a
combination of imaging, biochemical, and functional analyses in compartmentalized
neuronal cultures, as well as in vivo analyses in mice to accomplish this goal. These
studies will advance the knowledge of spatial modes of signaling in neurons that underlie
axon development, maintenance, and regeneration.
随着轴突的生长和生长,轴突不断对环境中的外部信号做出反应
在发育过程中导航到目标组织,并进行维护和修复
在成人生活中。MRNA定位和局部蛋白质合成是一种保守的机制,
允许对外部营养和引导提示做出快速和轴突自主的反应。
尽管轴突蛋白质合成的功能越来越受到重视,但在
我们的知识是了解新生蛋白质是如何进一步加工的
定位于轴突以产生全功能蛋白质。我们的初步结果表明
一种神经营养因子(神经生长因子)强烈地调节局部蛋白质的合成
以及轴突中新生成的蛋白质的脂化(苯丙基化)。人们一直认为
蛋白质预烯基化是一种结构性机制,它发生在整个细胞质和
对于细胞功能是允许的。与之形成鲜明对比的是,我们发现,在神经元中,苯丙基化
受到外部信号的精细时空控制。此应用程序的目标是
是确定耦合的轴突蛋白合成和预烯基化是否作为
调节机制定位和丰富轴突间的蛋白质,以确保
对外在促进生长线索的动态和空间反应。我们将使用
影像、生化和功能分析的组合
神经元培养,以及在老鼠体内的分析,以实现这一目标。这些
研究将推进对神经元信号空间模式的了解
轴突的发育、维持和再生。
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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Rejji Kuruvilla其他文献
Rejji Kuruvilla的其他文献
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{{ truncateString('Rejji Kuruvilla', 18)}}的其他基金
2023 Neurotrophic Mechanisms in Health and Disease
2023 健康与疾病中的神经营养机制
- 批准号:
10654336 - 财政年份:2023
- 资助金额:
$ 43.28万 - 项目类别:
Neuron-satellite glia interactions in the sympathetic nervous system
交感神经系统中神经元-卫星胶质细胞的相互作用
- 批准号:
10719545 - 财政年份:2023
- 资助金额:
$ 43.28万 - 项目类别:
2019 Neurotrophic Mechanisms in Health and Disease Gordon Research Conference
2019年健康与疾病中的神经营养机制戈登研究会议
- 批准号:
9755039 - 财政年份:2019
- 资助金额:
$ 43.28万 - 项目类别:
Neurotrophic factor trafficking and signaling in development and disease
发育和疾病中的神经营养因子运输和信号传导
- 批准号:
9897598 - 财政年份:2019
- 资助金额:
$ 43.28万 - 项目类别:
Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
- 批准号:
10056229 - 财政年份:2019
- 资助金额:
$ 43.28万 - 项目类别:
Neurotrophic factor trafficking and signaling in development and disease
发育和疾病中的神经营养因子运输和信号传导
- 批准号:
10377384 - 财政年份:2019
- 资助金额:
$ 43.28万 - 项目类别:
Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
- 批准号:
10534132 - 财政年份:2019
- 资助金额:
$ 43.28万 - 项目类别:
Sympathetic innervation in pancreatic development and function
胰腺发育和功能中的交感神经支配
- 批准号:
8751267 - 财政年份:2014
- 资助金额:
$ 43.28万 - 项目类别:
Sympathetic innervation in pancreatic development and function
胰腺发育和功能中的交感神经支配
- 批准号:
8890854 - 财政年份:2014
- 资助金额:
$ 43.28万 - 项目类别:
Neurotrophin mechanisms in neural development and disease
神经营养蛋白在神经发育和疾病中的机制
- 批准号:
8533037 - 财政年份:2011
- 资助金额:
$ 43.28万 - 项目类别:
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