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

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

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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 dynein regulation
动力蛋白调节机制
  • 批准号:
    10671717
  • 财政年份:
    2022
  • 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:
    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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