The PAR-6/aPKC Polarity Complex in Synaptic Assembly and Function
The PAR-6/aPKC Polarity Complex in Synaptic Assembly and Function
批准号:
8414161
负责人:
Huaye Zhang
金额:
$7.91万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-05-01 至 2013-06-30
关键词:
ActinsAddressAffectAlzheimer&aposs DiseaseAxonBehavioralBrainCell divisionCell surfaceCellsClinicalComplexDataDendritic SpinesEndocytosisEnvironmentEpithelialExcitatory SynapseGlutamate ReceptorGlutamatesGoalsGuanine Nucleotide Exchange FactorsGuanosine Triphosphate PhosphohydrolasesInstructionKnockout MiceMaintenanceMediatingMemoryMemory impairmentMental RetardationMentorsMolecularMonomeric GTP-Binding ProteinsMorphogenesisNervous System PhysiologyNeurodegenerative DisordersNeuronsPARD6A genePathway interactionsPhasePhosphorylationPoly(ADP-ribose) PolymerasesProcessProteinsRecyclingRegulationResearch ProposalsRoleSchizophreniaSignal PathwaySignal TransductionStructureSurfaceSynapsesSynaptic TransmissionSynaptic plasticityTestingTranslatingVertebral columnVesiclebasebrain cellcognitive functionin vivomigrationnervous system disordernovelresponsesynaptic functiontransmission process
中文摘要
这一建议是基于PAR-6/aPKC复合体调节树突棘的发现
形态发生,它通过一种新的信号通路实现这一点,涉及pi90 RhoGAP和RhoA
GTP酶。在该项目指导阶段的研究表明,小GTP酶Rnd1是一个候选
介导PAR-6/aPKC对p190RhoGAP和RhoA影响的蛋白质。本提案的目标1旨在
目的:阐明PAR-6/aPKC复合体调控RNDL的分子机制。具体地说,
PAR复合体对RND1表达和磷酸化的影响以及RND/190相互作用将是
检查过了。为了进一步研究PAR复合体在突触功能中的作用,我们将阐明
PAR复合体调节谷氨酸能突触传递的机制,并鉴定
PAR综合体的上游监管机构。最后,我们正在培育PAR-6C条件性基因敲除小鼠
验证PAR复合体参与体内突触可塑性和记忆形成的假设。我的
长期目标是了解调控树突棘形态发生的复杂信号机制
以及突触的可塑性,以及它们如何在体内转化为记忆的形成和维持。
英文摘要
The proposal is based on the finding that the PAR-6/aPKC complex regulates dendritic spine
morphogenesis, and it does so through a novel signaling pathway involving pi90 RhoGAP and the RhoA
GTPase. Studies during the mentored phase of this project revealed the small GTPase Rnd1 as a candidate
protein for mediating the effects of PAR-6/aPKC on p190RhoGAP and RhoA. Aim 1 of this proposal seeks
to elucidate the molecular mechanism by which the PAR-6/aPKC complex regulates Rndl. Specifically, the
effect of the PAR complex on Rndl expression and phosphorylation, and Rnd/190 interaction will be
examined. To further examine the role of the PAR complex in synaptic function, we will elucidate the
mechanisms by which the PAR complex regulates glutamatergic synaptic transmissioin, and identify the
upstream regulators of the PAR complex. Finally, we are generating PAR-6C conditional knockout mice to
test the hypothesis that the PAR complex is involved in synaptic plasticity and memory formation in vivo. My
long term goal is to understand the complex signaling mechanisms regulating dendritic spine morphogenesis
and synaptic plasticity, and how they translate to memory formation and maintenance in vivo.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:8203101
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依托单位:
The PAR-6/aPKC Polarity Complex in Synaptic Assembly and Function
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批准号:8209063
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资助金额:$24.9万
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负责人:Huaye Zhang
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依托单位:
The PAR-6/aPKC Polarity Complex in Synaptic Assembly and Function
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批准号:7642842
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项目类别:
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资助金额:$9.0万
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财政年份:2009
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负责人:Huaye Zhang
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依托单位:
海外基金