ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
批准号:
9264291
负责人:
Phyllis I Hanson
金额:
$37.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-01-01 至 2020-11-30
关键词:
ATP phosphohydrolaseAutomobile DrivingBindingBiogenesisCell divisionCell membraneCellular MembraneComplexCore ProteinCultured CellsCytoplasmDefectDendritesDiseaseElectron MicroscopyEvolutionExcisionFilamentFutureGolgi ApparatusHIV BuddingHereditary Spastic ParaplegiaHomoHumanIn VitroIndividualLysosomesMalignant NeoplasmsMediatingMembraneMembrane ProteinsModelingMolecularMolecular ConformationMorphologyMultivesicular BodyNerve DegenerationNuclear EnvelopeOrganellesPathway interactionsPhysiologicalPolymersProcessProteinsReactionRecyclingRoleScienceSorting - Cell MovementSurfaceSystemTestingVesicleViralWorkYeastschediak-higashi syndromefunctional groupin vivolate endosomemembrane modelpreferenceprotein complexprotein degradationprotein functionrepairedretrograde transporttrafficking
中文摘要
运输所需的内体分选复合体(ESCRT)机制是一组相互作用的蛋白质
英文摘要
The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is a set of interacting protein
complexes responsible for cargo selection and biogenesis of intralumenal vesicles inside endosomal
multivesicular bodies, also known as late endosomes. Evolutionary conservation and the discovery that
ESCRTs are required for topologically equivalent processes including viral budding, cytokinetic abscission,
and nuclear envelope closure led to the now widely accepted concept that ESCRTs are uniquely involved in
membrane fission for reactions that share this topology. ESCRT-III proteins act by changing conformation
and polymerizing into membrane-remodeling filaments that spiral on the inside – negatively curved –
surface of membrane tubules, ultimately pulling the tubules closed to drive membrane fission and release.
Intriguingly, there are twelve ESCRT-III proteins in humans that are not functionally interchangeable.
Beyond identification of different molecular binding partners, there has been little structural distinction
among these proteins to explain their unique physiological importance. We recently made the surprising
discovery that two human ESCRT-III proteins – CHMP1B and IST1 – assemble into filaments that spiral
around the outside – positively curved – surface of membrane tubules, forming external coats in vitro and in
vivo. This unexpected preference for positively curved membrane tubules challenges the dogma that the
membrane deforming and fission activity associated with ESCRT-III filaments is limited to a single topology
and prompts us to reconsider established paradigms for ESCRT-III function. This project will (1) define the
topology preference of particular ESCRT-III homo- and heteropolymers polymers and the corresponding
distribution of endogenous ESCRT-III proteins across the endosomal system, (2) establish the role(s) of
representative ESCRT-III proteins in distinct endosomal cargo trafficking pathways, and (3) compare the
effects of depleting different ESCRT-III proteins on endosomal and lysosomal morphology. This work will
expand our understanding of the ESCRT-III membrane remodeling system with significant implications for
future studies of trafficking and organization within the endolysosomal system.
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批准号:10214472
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项目类别:
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资助金额:$52.92万
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资助金额:$53.68万
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ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
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批准号:10447626
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资助金额:$39.59万
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批准号:10676296
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批准号:10683489
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批准号:10299123
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资助金额:$39.59万
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财政年份:2017
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负责人:Phyllis I Hanson
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依托单位:
NANOSCALE ARCHITECTURE OF ESCRT MACHINERY IN HIV RELEASE
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批准号:8993494
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项目类别:
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资助金额:$7.63万
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财政年份:2015
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负责人:Phyllis I Hanson
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依托单位:
MOLECULAR MECHANISMS OF MULTIVESICULAR BODY BIOGENESIS
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批准号:7923502
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项目类别:
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资助金额:$33.25万
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财政年份:2009
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负责人:Phyllis I Hanson
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依托单位:
MOLECULAR MECHANISMS OF MULTIVESICULAR BODY BIOGENESIS
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批准号:7921916
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项目类别:
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资助金额:$31.6万
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财政年份:2008
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负责人:Phyllis I Hanson
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依托单位:
MOLECULAR MECHANISMS OF MULTIVESICULAR BODY BIOGENESIS
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批准号:8134458
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项目类别:
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资助金额:$31.28万
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财政年份:2008
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负责人:Phyllis I Hanson
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依托单位:
MOLECULAR MECHANISMS OF MULTIVESICULAR BODY BIOGENESIS
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批准号:7590972
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项目类别:
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资助金额:$31.92万
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财政年份:2008
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负责人:Phyllis I Hanson
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依托单位:
MOLECULAR MECHANISMS OF MULTIVESICULAR BODY BIOGENESIS
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批准号:7692194
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项目类别:
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资助金额:$31.92万
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财政年份:2008
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负责人:Phyllis I Hanson
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依托单位:
Functional Analysis of TorsinA
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批准号:6830672
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项目类别:
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资助金额:$28.31万
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财政年份:2004
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负责人:Phyllis I Hanson
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依托单位:
Functional Analysis of TorsinA
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批准号:7090653
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项目类别:
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资助金额:$27.64万
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财政年份:2004
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负责人:Phyllis I Hanson
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依托单位:
FUNCTIONAL ANALYSIS OF TORSIN A
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批准号:8238273
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项目类别:
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资助金额:$33.25万
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财政年份:2004
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负责人:Phyllis I Hanson
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依托单位:
Functional Analysis of TorsinA
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批准号:7262442
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项目类别:
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资助金额:$26.84万
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财政年份:2004
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负责人:Phyllis I Hanson
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依托单位:
Functional Analysis of TorsinA
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批准号:6898700
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项目类别:
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资助金额:$28.31万
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财政年份:2004
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负责人:Phyllis I Hanson
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依托单位:
海外基金