Molecular mechanisms of spectrin-dependent axonal organization and function in cerebellar granule cells
小脑颗粒细胞血影蛋白依赖性轴突组织和功能的分子机制
基本信息
- 批准号:10605465
- 负责人:
- 金额:$ 3.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:ANK2 geneANK3 geneAnkyrinsAttention deficit hyperactivity disorderAttentional deficitAxonAxonal TransportBindingBiochemicalBiological AssayBrainCell Adhesion MoleculesCerebellar DiseasesCerebellumChildColonComplexCytoskeletonData AnalysesDendritesDevelopmentDevelopmental Delay DisordersDiseaseEarly DiagnosisElectrophysiology (science)EpilepsyEtiologyF-ActinFiberFrequenciesGeneticGlutamatesHippocampusHyperactivityImage AnalysisIndividualIntellectual functioning disabilityIon ChannelLeadMacromolecular ComplexesMembraneMembrane LipidsMembrane ProteinsMembrane Transport ProteinsMicroscopyMolecularMorphologyMotorMusNeurodevelopmental DisorderNeurologicNeurologic SymptomsNeuronsOrganellesOutputPatientsPlayPreparationProteinsReportingResearch Project GrantsResolutionRoleSCN2A proteinSamplingScientistSeizuresSignal TransductionSocial FunctioningSodium ChannelSpectrinStructureSynapsesSynaptic TransmissionSynaptic VesiclesSyndromeTechniquesTherapeutic InterventionTrainingVariantVesicleautism spectrum disordercognitive functioncomorbiditydesigngranule cellinsightlive cell imagingmultiple omicsmutantneuron componentneuronal excitabilityneurotransmissionnovelsuperresolution microscopytraffickingtraining opportunityvesicle transportvesicular releasevoltage
项目摘要
PROJECT SUMMARY
βII-spectrin (encoded by SPTBN1), is a ubiquitous component of the submembrane neuronal cytoskeleton. βII-
spectrin binds F-actin and ankyrins to organize complex networks of ion channels, membrane transporters and
cell adhesion molecules. βII-spectrin also promotes bidirectional transport of organelles and vesicles. Our lab
recently reported de novo SPTBN1 variants as the genetic cause of a developmental delay syndrome that is
comorbid with intellectual disability, autism spectrum disorder, ADHD, and seizures. However, the neuron types
and brain circuits most vulnerable to deficits in βII-spectrin function and their specific contribution to the diverse
neurological presentations are not fully elucidated. My preliminary studies indicate that βII-spectrin plays
important roles in modulating cerebellar function and that cerebellar dysfunction may contribute to the SPTBN1
syndrome. To begin to unravel the roles of βII-spectrin in the cerebellum, I will focus on investigating its function
in cerebellar granule cells by determining how βII-spectrin promotes: 1) the organization of excitable axonal
domains and 2) axonal organelle dynamics.
项目摘要
β II-血影蛋白(由SPTBN 1编码)是膜下神经元细胞骨架的普遍存在的组分。β Ⅱ-
血影蛋白结合F-肌动蛋白和锚蛋白,以组织离子通道、膜转运蛋白和
细胞粘附分子β II-血影蛋白还促进细胞器和囊泡的双向运输。我们实验室
最近报道,SPTBN 1的新生变异是一种发育迟缓综合征的遗传原因,
与智力残疾、自闭症谱系障碍、多动症和癫痫共病。然而,神经元类型
和脑回路最容易受到β II-血影蛋白功能缺陷的影响,以及它们对不同的
神经学表现尚未完全阐明。我的初步研究表明β II-血影蛋白
在调节小脑功能中起重要作用,小脑功能障碍可能导致SPTBN 1
综合征为了开始阐明β II-血影蛋白在小脑中的作用,我将重点研究其功能
通过确定β II-血影蛋白如何促进:1)可兴奋轴突的组织
结构域和2)轴突细胞器动力学。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Reginald James Edwards其他文献
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