Deciphering the cellular roles of LIS1 in the mature nervous system
解读 LIS1 在成熟神经系统中的细胞作用
基本信息
- 批准号:10586142
- 负责人:
- 金额:$ 18.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:ActinsAdolescentAdultAfferent NeuronsAspiration PneumoniaAstrocytesAutonomic DysfunctionAxonAxonal TransportBrainBrain DiseasesCardiac MyocytesCell DeathCellsCessation of lifeComplexCoupledCytoplasmDefectDendritic SpinesDevelopmentDynein ATPaseEpilepsyExploratory/Developmental GrantFutureGenetic RecombinationHumanInvestigationKnockout MiceKyphosis deformity of spineLIS1 proteinLegMeasuresMidbrain structureMitochondriaMolecularMolecular MotorsMonitorMotorMusMutationMyocardiumNerve DegenerationNervous SystemNeurogliaNeurologicNeuronsOrganellesPathologicPathologyPhenotypeProbabilityReportingRespirationRiskRodentRoleSeizuresSkeletal MuscleSourceSpinal CordStructureSudden DeathSymptomsSynapsesSynaptic TransmissionSynaptosomesTail SuspensionTamoxifenTimeWorkaxonal degenerationcell motilitycell typedynactinexperienceexperimental studyhindbraininsightlissencephalymouse modelpredictive modelingpromoterresponsesynaptic function
项目摘要
SUMMARY
LIS1 mutations can have major pathological effects on human brain development, but we have
only a minimal understanding of the postdevelopmental roles of LIS1. LIS1 regulates dynein, a
molecular motor that is vitally important for distributing organelles to specific regions in the cell.
Neurons in the mature nervous system have extremely long connections called axons that place
huge demands on transport motors like dynein. LIS1 depletion in adult mice has severe
consequences - mice rapidly develop neurological problems followed by death. We suspect that
these severe responses are caused by LIS1 loss in sensorimotor and cardiorespiratory circuits.
There was no detectable cell loss or nerve degeneration so we think the problems arise at the
level of the synapses, specialized structures that are critical for normal circuits. In Aim 1 we will
determine the molecular and cellular changes correlated with the pathological responses,
focusing on dynein motors, synapses, and mitochondria, an important dynein cargo. In Aim 2
we propose to deplete LIS1 specifically from neurons (Aim 2A) and a type of glial cell called an
astrocyte (Aim 2B). Both cell types express high levels of LIS1, and both contribute to normal
synaptic function. We will be able to determine if either are the cellular source of the severe
symptoms in the earlier mouse model, or if there are cell type specific symptoms. LIS1 has a
known role in axon transport but its function in mature astrocytes has been overlooked in the
field. This work will bring new insight into functions of LIS1 in the adult brain.
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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DEANNA S SMITH其他文献
DEANNA S SMITH的其他文献
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{{ truncateString('DEANNA S SMITH', 18)}}的其他基金
Deciphering the cellular roles of LIS1 in the mature nervous system
解读 LIS1 在成熟神经系统中的细胞作用
- 批准号:
10450281 - 财政年份:2022
- 资助金额:
$ 18.08万 - 项目类别:
Using LIS1 missense mutations to probe dynein regulatory mechanisms
利用 LIS1 错义突变探测动力蛋白调节机制
- 批准号:
10544530 - 财政年份:2022
- 资助金额:
$ 18.08万 - 项目类别:
Using LIS1 missense mutations to probe dynein regulatory mechanisms
利用 LIS1 错义突变探测动力蛋白调节机制
- 批准号:
10351719 - 财政年份:2022
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly protein, Lis1, in dynein-based transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
8235636 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly protein, Lis1, in dynein-based transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
8608604 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly protein, Lis1, in dynein-based transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
8618957 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly Protein, Lis1, in Dynein-Based Transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
7911470 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly Protein, Lis1, in Dynein-Based Transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
7370857 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly Protein, Lis1, in Dynein-Based Transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
8013510 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
Examining the role of the Lissencephaly Protein, Lis1, in Dynein-Based Transport
检查无脑畸形蛋白 Lis1 在基于动力蛋白的运输中的作用
- 批准号:
7544907 - 财政年份:2008
- 资助金额:
$ 18.08万 - 项目类别:
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