New Program Development Project
新程序开发项目
基本信息
- 批准号:7763457
- 负责人:
- 金额:$ 14.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:ActinsAddressAdhesionsAffectBehavioralBiochemicalBiological AssayBiotinylationBipolar DisorderBrainCadherinsCell AdhesionCell Adhesion MoleculesCellsCognition DisordersCognitiveComplexDendritesDendritic SpinesDevelopmentEphrin B ReceptorExcitatory SynapseFamilyFigs - dietaryFluorescence Resonance Energy TransferGenetic TranscriptionGrowthGrowth and Development functionGuanosine Triphosphate PhosphohydrolasesHippocampus (Brain)Homologous ProteinHumanImageImaging TechniquesImmunofluorescence ImmunologicIn VitroKnock-outKnockout MiceLearningLinkMaintenanceMediatingMemory impairmentMental RetardationMental Retardation and Developmental Disabilities Research CentersMolecularMorphogenesisMutant Strains MiceN-CadherinN-Methyl-D-Aspartate ReceptorsNervous system structureNeuronsPlayProcessProgram DevelopmentProtein BiosynthesisProteinsRNA InterferenceReceptor ActivationRegulationResolutionRoleSignal PathwaySignal TransductionSiteStagingStimulusSurfaceSynapsesSynaptic ReceptorsSyndromeTechniquesTestingVertebral columnabstractingdensityin vivoin vivo Modelinhibitor/antagonistinsightmembermutantnervous system developmentoverexpressionreceptor couplingresearch studyrhorho GTP-Binding Proteinsspatiotemporaltrafficking
项目摘要
REGULATORY MECHANISMS OF RAC-DEPENDENT DENDRITIC DEVELOPMENT AND
PLASTICITY
ABSTRACT
Formation of a functional nervous system requires the proper development and remodeling of dendrites and
dendritic spines, the primary sites of excitatory synapses in the brain. Rho family GTPases play critical roles in
regulating these processes. In particular, the Rho GTPase Rac promotes dendritic arborization and the
formation and maintenance of spines. Precise spatio-temporal regulation of Rac activity is essential for its
function, since aberrant Rac signaling results in dendrite and spine abnormalities and cognitive disorders
including mental retardation. Despite its importance, the mechanisms that regulate Rac signaling in neurons
remain pooriy understood. We previously identified the Rac-specific activator Tiami as a critical regulator of
dendrite, spine, and synapse development. We demonstrated that Tiami mediates both NMDA receptor-and
EphB receptor-dependent spine development by coupling these receptors to Rac signaling pathways that
control actin cytoskeletal remodeling and protein synthesis. Recently, we have also identified the Rac-specific
inhibitor Bcr as a Tiami-interacting protein that blocks Tiami-induced Rac activation and actin remodeling.
Overexpression and knockout experiments indicate that Bcr restricts the formation and growth of spines and
dendrites. The complex between Tiami and Bcr may serve as an "on-off switch" for precisely regulating Rac
signaling in neurons, which is essential for the proper formation and remodeling of spines, synapses, and
dendrites. To test this hypothesis, we propose the following specific aims: 1) to determine the role of Bcr in
restricting synapse development and dendritic growth; 2) to identify the mechanisms by which EphB and
NMDA receptors regulate the Tiami-Bcr complex, and determine the consequences on Rac activation and
synapse development; and 3) to elucidate the role of the Tiami-Bcr complex in regulating N-cadherinmediated
synaptic adhesion. To address these questions, we will use a multifaceted approach employing a
combination of molecular, cellular, biochemical, and high-resolution imaging techniques. Results from the
proposed studies will provide critical insight into the fundamental mechanisms that regulate Rac activation and
Rac-dependent synaptic and dendritic development in neurons, and help to elucidate how disruptions in Rac
GTPase signaling give rise to cognitive disorders such as mental retardation.
rac依赖性树突发育的调控机制
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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Kimberly R Tolias其他文献
Kimberly R Tolias的其他文献
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{{ truncateString('Kimberly R Tolias', 18)}}的其他基金
Adhesion-GPCRs: Regulators of dendritic development, synaptogenesis and mental health
粘附-GPCR:树突发育、突触发生和心理健康的调节因子
- 批准号:
9311432 - 财政年份:2017
- 资助金额:
$ 14.15万 - 项目类别:
Adhesion-GPCRs: Regulators of dendritic development, synaptogenesis and mental health
粘附-GPCR:树突发育、突触发生和心理健康的调节因子
- 批准号:
10088474 - 财政年份:2017
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rac-dependent Synaptic and Dendritic Development
调节 Rac 依赖性突触和树突发育的信号机制
- 批准号:
8488493 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rac-dependent Synaptic and Dendritic Development
调节 Rac 依赖性突触和树突发育的信号机制
- 批准号:
8289540 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rac-dependent Synaptic and Dendritic Development
调节 Rac 依赖性突触和树突发育的信号机制
- 批准号:
10191751 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rho GTPase-Dependent Synaptic Plasticity Underlying Memory in Health and Disease
调节健康和疾病记忆中 Rho GTP 酶依赖性突触可塑性的信号机制
- 批准号:
10587076 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rac-dependent Synaptic and Dendritic Development
调节 Rac 依赖性突触和树突发育的信号机制
- 批准号:
8085712 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
Signaling Mechanisms Regulating Rac-dependent Synaptic and Dendritic Development
调节 Rac 依赖性突触和树突发育的信号机制
- 批准号:
7740699 - 财政年份:2009
- 资助金额:
$ 14.15万 - 项目类别:
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