Molecular Interactions and Dynamics of the Yeast SPB Core Architecture
Molecular Interactions and Dynamics of the Yeast SPB Core Architecture
批准号:
8668223
负责人:
MARK WINEY
金额:
$10.14万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-09-01 至 2019-08-31
关键词:
AddressAffectAmino AcidsArchitectureBehaviorBindingBinding SitesBiological AssayBiological TestingBody SizeC-terminalCalmodulinCell CycleCell Cycle ArrestCellsCentrosomeChromosomal InstabilityChromosome SegregationChromosomesCollectionCompetenceComplementComplexCore ProteinCyclin-Dependent KinasesDataDefectDockingElectron MicroscopyEventGenesGrowthHomeostasisHumanIn VitroIndividualInterphaseLabelLeadLengthLibrariesMalignant NeoplasmsMapsMethodsMicrotubule-Organizing CenterMicrotubulesMitosisMitoticMitotic spindleModificationMolecular ModelsMonitorMutateMutationNamesNormal CellOrthologous GenePhosphoric Monoester HydrolasesPhosphorylationPhosphorylation SitePhosphotransferasesPhotobleachingPlayPloidiesPost-Translational Protein ProcessingProcessProtein KinaseProteinsPublishingRecoveryResourcesRoleSaccharomyces cerevisiaeSaccharomycetalesSignal TransductionStructureStudy modelsTestingThickTubulinUrsidae FamilyWorkYeastsbasecell typedata modelingdesignelectron tomographygamma Tubulinin vivointerestmolecular dynamicsmolecular modelingmutantneoplastic cellspindle pole bodytomography
中文摘要
中心体组织双极有丝分裂纺锤体,这是染色体分离和缺陷所必需的
英文摘要
Centrosomes organize the bipolar mitotic spindle, which is essential for chromosome segregation, and defects
in centrosomes lead to chromosomal instability and cancer in humans. The yeast centrosome (Spindle Pole
Body, SPB) shares many components and regulators with human centrosomes. Phosphorylation by Cyclin-
dependent kinase and Mpsl kinase is essential for both centrosome and SPB assembly and activity. In this
project in the PPG, we will determine structural features and phosphorylation events in core SPB components
that play significant roles in their assembly, function and exchange. To ascertain important functional domains
and residues, we will generate a library of mutations in SPB components based on two significant informational
resources: the first is structural data from Ivan Rayment (Project 3) on full-length SPB components or particular
domains. The second is phosphorylation sites mapped in vivo in our yeast SPB phosphoproteome. Mutated
SPB proteins will be tested for their competence in assembly into new SPBs at duplication and into existing
SPBs during mitosis when SPBs expand (mimicking centrosome maturation). They will also be evaluated for
compromised interactions with other SPB components and for structural perturbations as assayed by electron
microscopy and electron tomography. Candidate protein kinases, phosphatases and other regulators will be
screened for function with particular SPB components. It is anticipated that this work will expand the collection
of SPB regulatory molecules. Finally, despite evidence that components exchange in and out of SPBs during
the cell cycle, little is known about the mechanism of homeostasis. We will first determine the extent of SPB
size dynamics and component exchange in wild-type cells, using electron tomography and Fluorescent
Recovery After Photobleaching (FRAP). We will then use our mutant collection to assess the contribution of
particular features of individual SPB components to their exchange and attempt to identify trans-acting
regulators. This third aim will involve working closely with Davis (Project 2) on similar issues of SPB dynamics
and remodeling. Overall, we will provide an in vivo analysis of SPB components, bringing to bear our strengths
in electron microscopy and tomography to the PPG. We will contribute substantial in vivo analyses to test
hypotheses of SPB component behavior derived from structural studies and molecular modeling. Several of
the SPB components and regulators have human orthologs and studies in yeast will be critical to
understanding their assembly and function in the pericentriolar material (PCM) of centrosomes.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
MIPS (Microtubule Inner Proteins) function in cilia and basal bodies
-
批准号:10655224
-
项目类别:
-
资助金额:$35.65万
-
财政年份:2018
-
负责人:MARK WINEY
-
依托单位:
EFHC gene function in ciliary axomenes.
-
批准号:9900028
-
项目类别:
-
资助金额:$31.4万
-
财政年份:2018
-
负责人:MARK WINEY
-
依托单位:
EFHC gene function in ciliary axomenes.
-
批准号:10386664
-
项目类别:
-
资助金额:$11.76万
-
财政年份:2018
-
负责人:MARK WINEY
-
依托单位:
The Yeast Centrosome - Structure Assembly & Function
-
批准号:8668219
-
项目类别:
-
资助金额:$146.06万
-
财政年份:2014
-
负责人:MARK WINEY
-
依托单位:
The Yeast Centrosome - Structure Assembly & Function
-
批准号:9486545
-
项目类别:
-
资助金额:$107.21万
-
财政年份:2014
-
负责人:MARK WINEY
-
依托单位:
The Yeast Centrosome - Structure Assembly & Function
-
批准号:9073389
-
项目类别:
-
资助金额:$9.23万
-
财政年份:2014
-
负责人:MARK WINEY
-
依托单位:
Acquisition of a Transmission Electron Microscope
-
批准号:8246562
-
项目类别:
-
资助金额:$59.0万
-
财政年份:2012
-
负责人:MARK WINEY
-
依托单位:
SPINDLE POLE BODY PHOSPHOPROTEOME
-
批准号:8365899
-
项目类别:
-
资助金额:$2.65万
-
财政年份:2011
-
负责人:MARK WINEY
-
依托单位:
TETRAHYMENA BASAL BODY DUPLICATION
-
批准号:8362544
-
项目类别:
-
资助金额:$2.13万
-
财政年份:2011
-
负责人:MARK WINEY
-
依托单位:
SPINDLE POLE BODY PHOSPHOPROTEOME
-
批准号:8171462
-
项目类别:
-
资助金额:$0.38万
-
财政年份:2010
-
负责人:MARK WINEY
-
依托单位:
TETRAHYMENA BASAL BODY DUPLICATION
-
批准号:8170842
-
项目类别:
-
资助金额:$2.49万
-
财政年份:2010
-
负责人:MARK WINEY
-
依托单位:
Tetrahymena Basal Body Duplication
-
批准号:8035669
-
项目类别:
-
资助金额:$9.01万
-
财政年份:2010
-
负责人:MARK WINEY
-
依托单位:
Role of MPSI Kinase and Yeast Spindle Pole Cycle
-
批准号:7904475
-
项目类别:
-
资助金额:$12.48万
-
财政年份:2009
-
负责人:MARK WINEY
-
依托单位:
Tetrahymena Basal Body Duplication
-
批准号:7932442
-
项目类别:
-
资助金额:$5.33万
-
财政年份:2009
-
负责人:MARK WINEY
-
依托单位:
SPINDLE POLE BODY PHOSPHOPROTEOME
-
批准号:7957796
-
项目类别:
-
资助金额:$1.68万
-
财政年份:2009
-
负责人:MARK WINEY
-
依托单位:
TETRAHYMENA BASAL BODY DUPLICATION
-
批准号:7955064
-
项目类别:
-
资助金额:$2.14万
-
财政年份:2009
-
负责人:MARK WINEY
-
依托单位:
SPINDLE POLE BODY PHOSPHOPROTEOME
-
批准号:7723622
-
项目类别:
-
资助金额:$0.81万
-
财政年份:2008
-
负责人:MARK WINEY
-
依托单位:
TETRAHYMENA BASAL BODY PROTEOME
-
批准号:7723635
-
项目类别:
-
资助金额:$0.08万
-
财政年份:2008
-
负责人:MARK WINEY
-
依托单位:
TETRAHYMENA BASAL BODY DUPLICATION
-
批准号:7722856
-
项目类别:
-
资助金额:$0.92万
-
财政年份:2008
-
负责人:MARK WINEY
-
依托单位:
SPINDLE POLE BODY PHOSPHOPROTEOME
-
批准号:7602188
-
项目类别:
-
资助金额:$0.62万
-
财政年份:2007
-
负责人:MARK WINEY
-
依托单位:
海外基金