REGULATION OF ACTIN CAPPING PROTEIN
肌动蛋白加帽蛋白的调节
基本信息
- 批准号:8464156
- 负责人:
- 金额:$ 27.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-05-01 至 2016-02-29
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsActinsAddressAffectAgaricalesAmino Acid MotifsBindingBinding ProteinsBinding SitesBiochemicalBiological AssayC-terminalCD2-associated proteinCell physiologyCellsComplexCytoskeletonDefectDevelopmentFilamentGenesGoalsImmigrationIn VitroInflammatoryIntegrinsLeucine-Rich RepeatLifeLipidsLocationMembraneMembrane ProteinsMicrofilamentsMicroscopyModelingMolecularMolecular ConformationMovementMyosin ATPaseMyosin Type IPhenotypePhysiologicalPlus End of the Actin FilamentProcessProtein Binding DomainProtein IsoformsProteinsRNA Cap-Binding ProteinsRecruitment ActivityRegulationResearchRoleShapesSiteStructureSubcellular structureSurfaceTestingVertebratesWorkactin capping proteinbasecancer cellcell motilityhuman diseaseinhibitor/antagonistmutantnovelpreventresponse
项目摘要
Our goals are to elucidate the molecular mechanisms that control the assembly and
disassembly of actin filaments in cells and to understand how actin assembly dynamics contribute to
cell movement. The creation of free barbed ends of actin filaments is a critical determinant of actin
assembly, and capping those ends is necessary to produce force and movement at membranes. Here,
we investigate the function of the heterodimeric barbed-end capping protein (CP) and a set of
membrane-associated proteins that contain a conserved CP-binding motif, called CPI, but are
otherwise unrelated.
CARMIL, which contains the CPI motif and a second CP-binding motif, called CSI (CARMIL-
specific interacting), is a potent inhibitor of CP with the ability to create free barbed ends by uncapping
capped filaments. Uncapping is important because the turnover rates of CP and actin filaments in cells
are faster by orders of magnitude than those observed with purified proteins in vitro. Other CPI-motif
proteins, including CD2AP, Cin85, CKIP-1, WASHCAP(FAM21) and CapZIP bind CP but inhibit less
well, suggesting that they may target active CP to membrane compartments.
Aim 1: How Do Regulators of Capping Protein Work? To understand how CP regulation works, we
defined the actin-binding sites on CP, and we produced crystal structures for CP in complex with CP-
binding proteins. CPI motifs bind to a common site on CP at a distance from the actin-binding sites.
CARMIL binding causes an allosteric change in the conformation of the actin-binding sites. Now, we
ask whether the cellular function of the various CPI-motif proteins is to inhibit CP or to recruit active CP
to a location in the cell. In vitro, we will compare the abilities of the proteins to bind and inhibit CP in
biochemical assays with purified components. In cells, we will determine how targeting and
incorporation of CP into the actin cytoskeleton depends on the CP-interacting proteins and how their
interaction with CP affects local actin assembly and movement.
Aim 2: How Does CARMIL1 Function in Cells? CARMIL is important for cell migration and other actin-
related functions in metazoan cells. Vertebrates express three conserved CARMIL genes. We
discovered that CARMIL1 and CARMIL2 are both important for cell migration and that they have
distinct non-overlapping functions in a single migrating cell. CARMIL1 interacts with the dual-GEF Trio,
activates Rac1, and stimulates lamellipodia formation. We plan to investigate the molecular basis of
these phenotypes and interactions by a combination of localization, biochemical, knockdown, and
expression approaches.
COOPER, John A.
1R01 GM095509-01A1
我们的目标是阐明控制组装和组装的分子机制
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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JOHN A COOPER其他文献
JOHN A COOPER的其他文献
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{{ truncateString('JOHN A COOPER', 18)}}的其他基金
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10330809 - 财政年份:2022
- 资助金额:
$ 27.87万 - 项目类别:
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10797746 - 财政年份:2022
- 资助金额:
$ 27.87万 - 项目类别:
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10552651 - 财政年份:2022
- 资助金额:
$ 27.87万 - 项目类别:
Actin Assembly and Cell Motility: Mechanisms and Regulation
肌动蛋白组装和细胞运动:机制和调节
- 批准号:
9252484 - 财政年份:2016
- 资助金额:
$ 27.87万 - 项目类别:
Actin Assembly and Cell Motility: Mechanisms and Regulation
肌动蛋白组装和细胞运动:机制和调节
- 批准号:
9071730 - 财政年份:2016
- 资助金额:
$ 27.87万 - 项目类别:
Actin Assembly and Cell Motility: Mechanisms and Regulation
肌动蛋白组装和细胞运动:机制和调节
- 批准号:
9457467 - 财政年份:2016
- 资助金额:
$ 27.87万 - 项目类别:
Actin Assembly and Cell Motility: Mechanisms and Regulation
肌动蛋白组装和细胞运动:机制和调节
- 批准号:
9900809 - 财政年份:2016
- 资助金额:
$ 27.87万 - 项目类别:
ACTIN ASSEMBLY AND CELL MOTILITY: MECHANISMS AND REGULATION
肌动蛋白组装和细胞运动:机制和调节
- 批准号:
10075071 - 财政年份:2016
- 资助金额:
$ 27.87万 - 项目类别:
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肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
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