Mechanisms of Lis1 and NudE/L Regulation of the Molecular Motor Dynein
Lis1 和 NudE/L 分子运动动力蛋白的调节机制
基本信息
- 批准号:10087571
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:ATP HydrolysisATP phosphohydrolaseAdaptor Signaling ProteinAddressAffectAffinityAwardBindingBiochemistryBiotinylationCell CycleCell divisionCell physiologyCellsCellular biologyCopy Number PolymorphismCryoelectron MicroscopyDataData SetDiseaseDynein ATPaseGenesGoalsHealthHomologous GeneHumanImpairmentIn SituIn VitroInterphaseKnowledgeLearningMechanicsMentorsMicrocephalyMicroscopyMicrotubulesMitosisMitoticMolecular MotorsMotorMovementMutationNeurodegenerative DisordersNeuronsPathway interactionsPhasePhosphorylationPlayPlus End of the MicrotubulePost-Translational Protein ProcessingProcessProteinsProteomicsRecombinant ProteinsRegulationRegulatory PathwayResearchRoleSchizophreniaStructural ProteinStructureTechniquesTestingTrainingUnited States National Institutes of HealthWalkingWorkautism spectrum disorderbasecell motilitycell typedevelopmental diseaseexperimental studygenetic regulatory proteinhuman diseasein vitro activityinterdisciplinary approachlissencephalylive cell imagingmigrationnovelprotein complexprotein reconstitutionstructural biologytrafficking
项目摘要
PROJECT SUMMARY/ABSTRACT
Microtubule-based transport is required for cell division, cell migration, and for transport of a number of cellular
cargoes. A number of neurodevelopmental and neurodegenerative diseases are caused by or associated with
impaired microtubule-based transport. Cytoplasmic dynein 1 (dynein) is one of two molecular motor proteins
that are responsible for microtubule-based transport. Dynein is a highly regulated motor and interacts with a
number of adaptor proteins that modulate its function and activity. Mutations or copy number variations of
dynein regulatory proteins also leads to neurodevelopmental diseases. Despite the importance to human
health, mechanisms of how dynein is regulated are largely unknown. This proposal for an NIH K99/R00
Pathway to Independence Award seeks to understand how Lis1 and NudE/L, which are two regulators required
for nearly every dynein function, modulate dynein activity. Impaired Lis1 and NudE/L function is implicated in a
number of human diseases, including microcephaly, lissencephaly, schizophrenia, and autism. In Aim1 during
the mentored phase of the award, Dr. DeSantis will determine how Lis1 and NudE/L alter dynein function using
a combination of structural biology and pure protein reconstitution experiments. Phosphorylation of dynein,
Lis1, and NudE/L alter their activity but the mechanism of how this occurs in unknown. During the independent
phase of the award, Dr. DeSantis will also determine how post-translational modifications influence dynein,
Lis1, and NudE/L activity. In Aim 2, Dr. DeSantis will identify novel dynein regulatory pathways using a
combination of proteomics, cell biology, live cell imaging, and recombinant protein reconstitutions. Dr. DeSantis
has already identified novel Lis1 and NudE/L interacting proteins and will elucidate their function and
mechanism during the mentored and independent award phase. The results of this work will reveal
mechanisms of dynein regulation, which has far reaching implications in human health and disease. Dr.
DeSantis will receive training in cryo-electron microscopy in the K99 portion of the award. When combined with
her background in biochemistry, cell biology, and live cell imaging, learning cryo-electron microscopy will
empower Dr. DeSantis' research about mechanisms of motor protein regulation far beyond the duration of the
K99/R00 award.
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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Morgan DeSantis其他文献
Morgan DeSantis的其他文献
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{{ truncateString('Morgan DeSantis', 18)}}的其他基金
Mechanisms of Lis1 and NudE/L Regulation of the Molecular Motor Dynein
Lis1 和 NudE/L 分子运动动力蛋白的调节机制
- 批准号:
10374042 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
Mechanisms of Lis1 and NudE/L Regulation of the Molecular Motor Dynein
Lis1 和 NudE/L 分子运动动力蛋白的调节机制
- 批准号:
9762944 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
Mechanisms of Lis1 and NudE/L Regulation of the Molecular Motor Dynein
Lis1 和 NudE/L 分子运动动力蛋白的调节机制
- 批准号:
10132347 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
Optimizing and defining the mechanism of alpha-synuclein disaggregation by Hsp104
优化和定义 Hsp104 α-突触核蛋白解聚机制
- 批准号:
8514957 - 财政年份:2012
- 资助金额:
$ 24.9万 - 项目类别:
Optimizing and defining the mechanism of alpha-synuclein disaggregation by Hsp104
优化和定义 Hsp104 α-突触核蛋白解聚机制
- 批准号:
8316617 - 财政年份:2012
- 资助金额:
$ 24.9万 - 项目类别:
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