REGULATION OF GLUTAMATERGIC SYNAPSES BY LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN
富含亮氨酸重复跨膜蛋白对谷氨酸突触的调节
基本信息
- 批准号:7767459
- 负责人:
- 金额:$ 32.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-01-15 至 2013-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAutistic DisorderAxonBrainCell Surface ProteinsCellsChildhood Neurological DisorderCoculture TechniquesDefectDendritic SpinesDevelopmentDiseaseExcitatory SynapseFrequenciesGlutamatesGoalsHippocampus (Brain)Integral Membrane ProteinLeucine-Rich RepeatLinkMental RetardationMolecularMorphogenesisMorphologyMutationN-Methyl-D-Aspartate ReceptorsNeuronsPlayPopulationProbabilityPropertyRegulationRett SyndromeRoleSeriesSpecific qualifier valueStructureSynapsesTertiary Protein StructureTherapeuticTimeVertebral columncell typedentate gyrusextracellularhippocampal pyramidal neuronin vivomossy fiberpostsynapticpresynapticpublic health relevanceresearch studysmall hairpin RNAsynaptogenesis
项目摘要
DESCRIPTION (provided by applicant): Our long-term goal is to gain a molecular understanding of the mechanisms that regulate the development and function of glutamatergic synapses in the mammalian brain. Most glutamatergic synapses share certain features, such as the presence of postsynaptic AMPA and NMDA receptors. At the same time, there is great diversity in the structure and function of glutamatergic synapses depending on the identity of the pre- and postsynaptic neuron. For example, CA3 neurons in the hippocampus receive highly facilitating mossy fiber synapses from Dentate Gyrus (DG) axons on specialized spines, called thorny excrescences. The same neurons receive association/commissural (A/C) neuron synapses on classical spines that are not highly facilitating. The CA3 A/C synapses share many structural features and functional properties with CA3-CA1 Schaffer collateral synapses, suggesting that they may be specified by common molecular mechanisms. Our preliminary studies suggest that the leucine rich repeat containing transmembrane protein LRRTM2 plays a critical role in regulating glutamatergic synapses in the hippocampus. In this proposal we wish to determine if LRRTM2 regulates specific classes of glutamatergic synapses in the hippocampus, and whether it regulates synapse structure and function in vivo. PUBLIC HEALTH RELEVANCE: The goal of this project is to understand the role of a class of cell surface proteins in the establishment and function of excitatory synaptic connections. Several childhood neurological disorders, such as Autism, Rett Syndrome, and X-linked mental retardation are characterized by defects in synaptic connectivity and function. The findings of this project should guide efforts to better understand and develop therapeutic strategies for these disorders.
描述(由申请人提供):我们的长期目标是从分子角度了解调节哺乳动物大脑中谷氨酸突触的发育和功能的机制。大多数谷氨酸能突触具有某些共同特征,例如突触后 AMPA 和 NMDA 受体的存在。同时,谷氨酸能突触的结构和功能存在很大差异,具体取决于突触前和突触后神经元的身份。例如,海马体中的 CA3 神经元从特殊棘上的齿状回 (DG) 轴突(称为棘赘生物)接收高度促进的苔藓纤维突触。相同的神经元在不太方便的经典棘上接收关联/连合(A/C)神经元突触。 CA3 A/C 突触与 CA3-CA1 Schaffer 侧支突触共享许多结构特征和功能特性,表明它们可能由共同的分子机制指定。我们的初步研究表明,富含亮氨酸重复序列的跨膜蛋白 LRRTM2 在调节海马谷氨酸突触中发挥着关键作用。在本提案中,我们希望确定 LRRTM2 是否调节海马中特定类别的谷氨酸突触,以及它是否调节体内突触结构和功能。公共健康相关性:该项目的目标是了解一类细胞表面蛋白在兴奋性突触连接的建立和功能中的作用。一些儿童神经系统疾病,例如自闭症、雷特综合症和 X 连锁智力低下,其特征是突触连接和功能缺陷。该项目的研究结果应指导更好地理解和制定这些疾病的治疗策略。
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)
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ANIRVAN GHOSH其他文献
ANIRVAN GHOSH的其他文献
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{{ truncateString('ANIRVAN GHOSH', 18)}}的其他基金
TOWARDS THE COMPLETE CHARACTERIZATION OF NEUREXIN TRANS-SYNAPTIC LIGANDS
神经毒素跨突触配体的完整表征
- 批准号:
8365894 - 财政年份:2011
- 资助金额:
$ 32.62万 - 项目类别:
REGULATION OF HIPPOCAMPAL CONNECTIVITY BY NEUROD2 MEDIATED TRANSCRIPTION
NEUROD2 介导的转录对海马连接的调节
- 批准号:
8361917 - 财政年份:2011
- 资助金额:
$ 32.62万 - 项目类别:
REGULATION OF GLUTAMATERGIC SYNAPSES BY LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN
富含亮氨酸重复跨膜蛋白对谷氨酸突触的调节
- 批准号:
8206744 - 财政年份:2010
- 资助金额:
$ 32.62万 - 项目类别:
REGULATION OF HIPPOCAMPAL CONNECTIVITY BY NEUROD2 MEDIATED TRANSCRIPTION
NEUROD2 介导的转录对海马连接的调节
- 批准号:
8169617 - 财政年份:2010
- 资助金额:
$ 32.62万 - 项目类别:
REGULATION OF GLUTAMATERGIC SYNAPSES BY LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN
富含亮氨酸重复跨膜蛋白对谷氨酸突触的调节
- 批准号:
8403596 - 财政年份:2010
- 资助金额:
$ 32.62万 - 项目类别:
REGULATION OF GLUTAMATERGIC SYNAPSES BY LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN
富含亮氨酸重复跨膜蛋白对谷氨酸突触的调节
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8013632 - 财政年份:2010
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Analysis of Neural Circuits using a Genetically-encoded Silencer
使用基因编码消音器分析神经回路
- 批准号:
7937912 - 财政年份:2009
- 资助金额:
$ 32.62万 - 项目类别:
Role of AMPA Receptor Reverse Signaling in Synapse Stability
AMPA 受体反向信号传导在突触稳定性中的作用
- 批准号:
8063182 - 财政年份:2009
- 资助金额:
$ 32.62万 - 项目类别:
Molecular and Cellular Mechanisms underlying function and dysfunction of Neural C
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- 批准号:
7859550 - 财政年份:2009
- 资助金额:
$ 32.62万 - 项目类别:
Role of AMPA Receptor Reverse Signaling in Synapse Stability
AMPA 受体反向信号传导在突触稳定性中的作用
- 批准号:
7731046 - 财政年份:2009
- 资助金额:
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