Regulation of membrane trafficking by Coronins
Coronins 对膜运输的调节
基本信息
- 批准号:10210757
- 负责人:
- 金额:$ 33.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:Actin-Binding ProteinActinsAddressAdhesionsAffectAutomobile DrivingAutophagocytosisAutophagosomeBindingBiochemicalBiological AssayBiological ProcessBiophysicsCell ShapeCell physiologyCellsCellular biologyComplexCrystallizationCrystallographyCytoskeletonDataDistantFamilyFluorescenceGeneticGlia Maturation FactorImageImaging TechniquesIn VitroIndividualIntracellular MembranesLeadLearningLengthLightLysosomesMediatingMembraneMicrofilamentsModelingMolecularNatural ImmunityNeuronsNutrientOrganellesPhagocytosisPlayProcessProtein BiochemistryProteinsPyrenesRecoveryRegulationResolutionRoleSeriesSpecificitySpeedStructureSurfaceSystemTailTechniquesTestingTimeTotal Internal Reflection FluorescentTransmembrane TransportVesicleWorkbasecell motilitycoronin proteingenetic regulatory proteinimmunological synapse formationinsightinterdisciplinary approachlive cell imagingmisfolded proteinneurotransmissionoverexpressionreconstructionsingle moleculespatiotemporaltraffickingwound healing
项目摘要
ABSTRACT
The extensive family of the Coronins plays an important role in regulating the actin
networks that drive cell migration, polarity, cell shape and intracellular trafficking, and
thereby contribute to essential biological processes ranging from innate immunity to
neuronal signaling. However, these functions and activities have been characterized for
the canonical Coronins. In stark contrast, we know next to nothing about the cellular
roles and actin cytoskeleton regulation of the structurally distinct class of the tandem
Coronins, which comprises Coronin 7 (Coro7), POD-1, and CorB. Our preliminary data
show that mammalian Coro7 can control Arp2/3-mediated nucleation, although the
mechanism underlying this activity remains elusive. In addition, we show that this actin-
regulatory activity can regulate NPF-induced actin networks that drive intracellular
membrane transport, including autophagy, a process used by cells to dispose of
unwanted organelles, misfolded proteins and toxic aggregates. Using a multidisciplinary
approach comprising state-of-the-art biochemical, biophysical, genetic and live-imaging
techniques we propose here to elucidate 1) how Coro7 structurally interacts with Arp2/3,
2) how Coro7 mechanistically inhibits Arp2/3-mediated nucleation by nucleation
promoting factors, and 3) by other Arp2/3 regulators, and 4) how these actin-regulatory
activities of Coro7 regulate the turnover of the branched actin networks that drive
autophagy.
摘要
Coronins家族在调节肌动蛋白中起着重要的作用
驱动细胞迁移、极性、细胞形状和细胞内运输的网络,以及
从而有助于从先天免疫到
神经信号然而,这些职能和活动的特点是,
典型的科罗尼。与此形成鲜明对比的是,我们对细胞的
作用和肌动蛋白细胞骨架调节的结构不同类的串联
冠蛋白,其包括冠蛋白7(Coro 7)、POD-1和CorB。我们的初步数据
表明哺乳动物Coro 7可以控制Arp 2/3介导的成核,尽管
这一活动背后的机制仍然难以捉摸。此外,我们表明,这种肌动蛋白-
调节活性可以调节NPF诱导的肌动蛋白网络,
膜运输,包括自噬,细胞使用的过程,以处置
不需要的细胞器、错误折叠的蛋白质和有毒聚集体。采用多学科
包括最先进的生物化学、生物物理学、遗传学和实时成像的方法
我们在这里提出的技术来阐明1)Coro 7如何在结构上与Arp 2/3相互作用,
2)Coro 7如何通过成核机制抑制Arp 2/3介导的成核
促进因子,3)其他Arp 2/3调节因子,以及4)这些肌动蛋白调节因子
Coro 7的活动调节分支肌动蛋白网络的周转,
自噬
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)
专利数量(0)
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Silvia Jansen其他文献
Silvia Jansen的其他文献
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{{ truncateString('Silvia Jansen', 18)}}的其他基金
Regulation of membrane trafficking by Coronins
Coronins 对膜运输的调节
- 批准号:
10398239 - 财政年份:2021
- 资助金额:
$ 33.08万 - 项目类别:
Regulation of membrane trafficking by Coronins
Coronins 对膜运输的调节
- 批准号:
10797956 - 财政年份:2021
- 资助金额:
$ 33.08万 - 项目类别:
Regulation of membrane trafficking by Coronins
Coronins 对膜运输的调节
- 批准号:
10605206 - 财政年份:2021
- 资助金额:
$ 33.08万 - 项目类别:
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