Mechanisms of Golgi Vesiculation during Mitosis
有丝分裂期间高尔基体形成水泡的机制
基本信息
- 批准号:7260190
- 负责人:
- 金额:$ 34.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-02-01 至 2008-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAntimitotic AgentsBindingC-terminalCell CycleCell Cycle CheckpointCellsClassCollectionDimensionsDrosophila genomeElementsEndoplasmic ReticulumEnzymesEventG-Protein-Coupled ReceptorsGenomeGolgi ApparatusGuanosine Triphosphate PhosphohydrolasesHandHomologous GeneHumanLibrariesLipaseMAP Kinase GeneMAP2K1 geneMammalian CellMembraneMembrane ProteinsMitogen-Activated Protein KinasesMitosisMitoticMitotic spindleMolecular MotorsNumbersOrganellesPathway interactionsPhosphoric Monoester HydrolasesPhosphorylationPhosphotransferasesProcessProtein BindingProtein DephosphorylationProtein IsoformsProteinsRNA SplicingRecruitment ActivityRegulationReportingResearch PersonnelRoleScreening procedureSignal TransductionTestingVariantVesicleWorkdaughter cellhuman PLK1 proteinnovelnumb proteinpreventprogramstransmission process
项目摘要
DESCRIPTION (provided by applicant): The pericentriolar inter connected stacks of Golgi cisternae are fragmented in mitotic mammalian cells. Why do these membranes undergo such a drastic change in their organization and by what mechanism? Do Golgi membranes fuse with the endoplasmic reticulum (ER) during mitosis and therefore use ER for their transmission into daughter cells? Our recent findings reveal that Golgi membranes do not fuse with the ER during mitosis. These findings resolve a long-standing controversy. We have found that inhibiting Golgi fragmentation prevents entry into mitosis. We have proposed the existence of a Golgi membrane specific cell-cycle checkpoint. We have found that kinases MEK1 and Polo like kinase (Plk); and Golgi associated proteins GRASP55 and GRASP65 are required for Golgi fragmentation. Our hypothesis is that MEK1 activates a novel spliced variant of ERK called ERK1c, which phosphorylates GRASP55 to disconnect Golgi stacks. This event occurs in G2 and it is necessary for entry into mitosis. Plk on the other hand, we suggest phosphorylates GRASP65. The phosphorylated GRASP65 recruits a novel protein called Gip (GRASP interacting protein) and this event is necessary for GRASP65 dependent regulation of spindle dynamics in mitosis. A new screen has revealed a number of proteins that regulate the dimensions of Golgi stacks and our hypothesis is that these proteins are modified (by phosphorylation/dephosphorylation) to reorganize Golgi membranes during mitosis. Finally, we are screening 5000 human enzymes (kinase, phosphatase, lipases, GTPases etc) to identify components that control, through the organization of Golgi apparatus, entry of cells into mitosis. Our findings will reveal the mechanism by which, cells duplicate their essential organelles during the cell cycle, and how Golgi membranes in turn through their organization, control mitotic entry
描述(由申请人提供):在有丝分裂的哺乳动物细胞中,高尔基池的中心周围相互连接的堆叠被破碎。为什么这些细胞膜的组织会发生如此剧烈的变化,是通过什么机制发生的?高尔基体膜是否在有丝分裂过程中与内质网融合,从而利用内质网将其传递到子细胞中?我们最近的研究结果表明,高尔基体膜不融合与ER在有丝分裂。这些发现解决了一个长期存在的争议。我们已经发现,抑制高尔基体断裂阻止进入有丝分裂。我们提出了一个高尔基体膜特异性细胞周期检查点的存在。我们发现,激酶MEK 1和波罗样激酶(Plk)以及高尔基体相关蛋白GRASP 55和GRASP 65是高尔基体片段化所必需的。我们的假设是,MEK 1激活了一种新的ERK剪接变体,称为ERK 1c,它磷酸化GRASP 55以断开高尔基体。这一事件发生在G2期,是进入有丝分裂所必需的。另一方面,我们建议磷酸化GRASP 65。磷酸化的GRASP 65招募一种新的蛋白质称为Gip(GRASP相互作用蛋白),这一事件是必需的GRASP 65依赖性调节纺锤体动力学在有丝分裂。一个新的屏幕已经揭示了一些蛋白质,调节高尔基体堆栈的尺寸和我们的假设是,这些蛋白质被修改(通过磷酸化/去磷酸化),以重组高尔基体膜在有丝分裂。最后,我们正在筛选5000种人类酶(激酶、磷酸酶、脂肪酶、GTP酶等),以确定通过高尔基体的组织控制细胞进入有丝分裂的组分。我们的发现将揭示细胞在细胞周期中复制其基本细胞器的机制,以及高尔基体膜如何通过其组织反过来控制有丝分裂进入
项目成果
期刊论文数量(2)
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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VIVEK MALHOTRA其他文献
VIVEK MALHOTRA的其他文献
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{{ truncateString('VIVEK MALHOTRA', 18)}}的其他基金
Mechanisms of Golgi Vesiculation during Mitosis
有丝分裂期间高尔基体形成水泡的机制
- 批准号:
6847190 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
MECHANISMS OF GOLGI VESICULATION DURING MITOSIS
有丝分裂过程中高尔基体形成的机制
- 批准号:
2776052 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
Mechanisms of Golgi Vesiculation during Mitosis
有丝分裂期间高尔基体形成水泡的机制
- 批准号:
6582730 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
Mechanisms of Golgi Vesiculation during Mitosis
有丝分裂期间高尔基体形成水泡的机制
- 批准号:
6699338 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
Mechanisms of Golgi Vesiculation during Mitosis
有丝分裂期间高尔基体形成水泡的机制
- 批准号:
7025091 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
MECHANISMS OF GOLGI VESICULATION DURING MITOSIS
有丝分裂过程中高尔基体形成的机制
- 批准号:
6351203 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
MECHANISMS OF GOLGI VESICULATION DURING MITOSIS
有丝分裂过程中高尔基体形成的机制
- 批准号:
6151027 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
MECHANISMS OF GOLGI VESICULATION DURING MITOSIS
有丝分裂过程中高尔基体形成的机制
- 批准号:
6498778 - 财政年份:1999
- 资助金额:
$ 34.85万 - 项目类别:
ID & CHAR OF DRUGS WHICH PERTURB GOLGI MORPHOLOGY IN MAMMALIAN CELLS
ID
- 批准号:
6252917 - 财政年份:1997
- 资助金额:
$ 34.85万 - 项目类别:
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