The relationship between Rab11-endosomes and the centrosome during division

Rab11-核内体和中心体在分裂过程中的关系

基本信息

  • 批准号:
    10205095
  • 负责人:
  • 金额:
    $ 31.5万
  • 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:
    2018-07-03 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

SUMMARY STATEMENT: Ciliopathies comprise a group of disorders associated with genetic mutations encoding defective proteins, which result in either abnormal formation or function of cilia. Ciliopathies have been linked to defects in molecular pathways organized at the primary cilium's basal body/centrosome and the primary cilium itself. Patients suffering from ciliopathies can display defects in left/right asymmetry, congenital cardiac defects, and formation of cysts in multiple organs including liver, pancreas and kidney. In vertebrates, motile cilia located in an organ of asymmetry play an important role in left-right development. Evidence from model organisms, such as zebrafish organ of asymmetry (Kupffer's Vesicle, KV), indicates that conserved cilia-driven left-right flow establishes left- right signals to regulate target genes to control left/right asymmetry. This project addresses the question: How do ciliated cells develop into a functional polarized organ? We propose this occurs through a sequential process that starts with cell division, polarity formation, and finishes with cilia assembly. If a ciliated organ wants to expand its central lumen, cells need to re-enter the cell cycle and correctly position its mitotic spindle along the longest axis parallel to the expanding lumen. We found that both Rab11-associated endosomes and a centrosome protein, cenexin, regulate the positioning of the mitotic spindle and ciliogenesis (Hehnly and Doxsey, 2014; Hung et al., 2016), but whether they act together during these processes has not been examined. During interphase, Rab11-endosomes associate with mother centriole sub-distal appendages where cenexin resides (Hehnly et al., 2012). Rab11 and a second GTPase, Rab8, can directly interact with cenexin. In addition, a GTPase cascade has been identified between Rab11 and Rab8 during ciliogenesis and apical membrane initiation, but if it requires the centrosome or occurs during specific points of the cell cycle is unknown. We will test the overall hypothesis that anchoring Rab11 and/or Rab8 by the mother centriole appendage protein, cenexin, is required for spindle positioning, polarity formation and/or ciliogenesis. To test this we will determine whether the centrosome can modulate Rab11 and/or Rab8 activity (Aim 1) and determine when during the cell cycle Rab11 and Rab8 activity is required to regulate tissue morphogenesis (Aim 2). This will be accomplished by using a 3-D kidney epithelial cell culture model and an in vivo developmental model, zebrafish KV formation, to identify a framework for how polarity formation relates to the cell cycle.!
综述:纤毛病包括一组与遗传相关的疾病

项目成果

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Heidi Hehnly其他文献

Heidi Hehnly的其他文献

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{{ truncateString('Heidi Hehnly', 18)}}的其他基金

Cell cycle dependent mechanisms triggering lumen formation in vivo
触发体内管腔形成的细胞周期依赖性机制
  • 批准号:
    10322191
  • 财政年份:
    2021
  • 资助金额:
    $ 31.5万
  • 项目类别:
Cell cycle dependent mechanisms triggering lumen formation in vivo
触发体内管腔形成的细胞周期依赖性机制
  • 批准号:
    10531276
  • 财政年份:
    2021
  • 资助金额:
    $ 31.5万
  • 项目类别:
The relationship between Rab11-endosomes and the centrosome during division
Rab11-核内体和中心体在分裂过程中的关系
  • 批准号:
    10431951
  • 财政年份:
    2018
  • 资助金额:
    $ 31.5万
  • 项目类别:
The relationship between Rab11-endosomes and the centrosome during division
Rab11-核内体和中心体在分裂过程中的关系
  • 批准号:
    9892164
  • 财政年份:
    2018
  • 资助金额:
    $ 31.5万
  • 项目类别:
Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis.
母中心粒附属物调节 AMIS 区室和纤毛发生。
  • 批准号:
    8727084
  • 财政年份:
    2013
  • 资助金额:
    $ 31.5万
  • 项目类别:
Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis.
母中心粒附属物调节 AMIS 区室和纤毛发生。
  • 批准号:
    8568272
  • 财政年份:
    2013
  • 资助金额:
    $ 31.5万
  • 项目类别:
Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis
母中心粒附属物调节 AMIS 区室和纤毛发生
  • 批准号:
    9815492
  • 财政年份:
    2013
  • 资助金额:
    $ 31.5万
  • 项目类别:
Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis.
母中心粒附属物调节 AMIS 区室和纤毛发生。
  • 批准号:
    9314596
  • 财政年份:
    2013
  • 资助金额:
    $ 31.5万
  • 项目类别:
Molecular mechanism of exocyst-centriolin complexes in abscission
外囊-中心蛋白复合物脱落的分子机制
  • 批准号:
    8145674
  • 财政年份:
    2010
  • 资助金额:
    $ 31.5万
  • 项目类别:
Molecular mechanism of exocyst-centriolin complexes in abscission
外囊-中心蛋白复合物脱落的分子机制
  • 批准号:
    8003744
  • 财政年份:
    2010
  • 资助金额:
    $ 31.5万
  • 项目类别:
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