Investigation of TRIM9 in cell shape change in the aging brain
Investigation of TRIM9 in cell shape change in the aging brain
批准号:
10121328
负责人:
Stephanie Gupton
金额:
$19.94万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-12-01 至 2024-11-30
关键词:
ActinsAdultAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAnti-Inflammatory AgentsAreaAssesAutopsyAxonBiological AssayBiotinBrainCell ShapeCellsCharacteristicsCollaborationsDCC geneDataDendritic SpinesDevelopmentDisease ProgressionExhibitsFunctional disorderFundingFutureGenesGoalsGrowth ConesHealthHippocampus (Brain)HumanImmunohistochemistryImpaired cognitionInvestigationIschemic StrokeLearningLewy Body DementiaLigationMass Spectrum AnalysisMelanoma CellMembraneMemoryMorphogenesisMorphologyMusNational Institute of General Medical SciencesNervous system structureNeuronsOntologyParaneoplastic Cerebellar DegenerationParentsParkinson&aposs DementiaPathologyPatientsPhysiologyPlayPolymerasePost-Translational Protein ProcessingPredispositionProtein IsoformsProteinsRegulationResearchRoleShapesSynapsesUbiquitinationWild Type MouseWorkaging brainbasedensityexperimental studyfollow-upinterestmouse modelnetrin receptorneuroinflammationnovelnovel markeroverexpressionparalogous genepostsynapticresponsesynaptic functiontarget SNARE proteinstau Proteinstau aggregationtau-1ubiquitin-protein ligasevasodilator-stimulated phosphoprotein
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Over the past nine years, my lab has focused on the function of the brain enriched E3 ubiquitin
ligase TRIM9. Our interest in TRIM9 originated from our identification of direct interactions
between TRIM9 and the actin polymerase VASP, the exocytic synaptic t-SNARE SNAP25 and
the netrin receptor DCC. This led us to hypothesize that TRIM9 coordinated cytoskeletal and
membrane remodeling during netrin triggered cellular shape change. Our work has shown that
TRIM9 regulates cytoskeletal dynamics and membrane remodeling during several critical stages
of morphogenesis of developing neurons. This includes not only changes in developmentally
relevant stages such as growth cone morphology, and axonal and dendritic branching, but later
morphogenetic stages with synaptic function relevance, such as dendritic spine density. Several
lines of evidence suggest that TRIM9 may continue to play a critical role in the health and function
of the aging neuron. First, TRIM9 enrichment in nervous system continues into adult and is
repressed in the brains of human patients with Parkinson's disease and dementia with Lewy
bodies. Our work has shown that deletion of murine Trim9 results in dramatic cognitive
impairment, specifically in spatial learning and memory. Trim9-deficient mice exhibit increased
neuroinflammation, whereas increasing TRIM9 expression plays neuroprotective roles following
ischemic stroke. Finally, TRIM9 is a novel marker for paraneoplastic cerebellar degeneration.
Here, we propose to expand our investigation into how TRIM9 specifically affects the shape and
function of the aging neuron, and susceptibility to AD.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Netrin Glycosylation Influences Chemotaxis and Haptotaxis
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批准号:10665243
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项目类别:
-
资助金额:$19.44万
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财政年份:2023
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负责人:Stephanie Gupton
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依托单位:
Exploring The Brain Enriched E3 Ubiquitin Ligase TRIM9 in Alzheimer's Disease
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批准号:10467201
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项目类别:
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资助金额:$42.76万
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财政年份:2022
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负责人:Stephanie Gupton
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依托单位:
Super Resolution STED Microscopy at UNC
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批准号:10414283
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项目类别:
-
资助金额:$60.0万
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财政年份:2022
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负责人:Stephanie Gupton
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依托单位:
Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
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批准号:10306344
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项目类别:
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资助金额:$38.03万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Exocytosis fuels plasma membrane expansion in developing neurons
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批准号:10402882
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项目类别:
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资助金额:$38.4万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
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批准号:10063996
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项目类别:
-
资助金额:$38.03万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Exocytosis fuels plasma membrane expansion in developing neurons
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批准号:10159320
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项目类别:
-
资助金额:$38.4万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Administrative Equipment Supplement for GM135160
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批准号:10387434
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项目类别:
-
资助金额:$9.0万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Undergraduate Research: Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
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批准号:10586656
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项目类别:
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资助金额:$0.95万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Supplement to Support Diversity in Research
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批准号:10596422
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项目类别:
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资助金额:$1.57万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
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批准号:10531200
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项目类别:
-
资助金额:$38.03万
-
财政年份:2019
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负责人:Stephanie Gupton
-
依托单位:
Exocytosis fuels plasma membrane expansion in developing neurons
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批准号:10617331
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项目类别:
-
资助金额:$38.4万
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财政年份:2019
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负责人:Stephanie Gupton
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依托单位:
TRIM9 coordinates membrane trafficking and cytoskeletal dynamics
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批准号:8788420
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项目类别:
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资助金额:$28.73万
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财政年份:2014
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负责人:Stephanie Gupton
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依托单位:
TRIM9 coordinates membrane trafficking and cytoskeletal dynamics
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批准号:8991497
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项目类别:
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资助金额:$35.0万
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财政年份:2014
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负责人:Stephanie Gupton
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依托单位:
海外基金