Polpeptides of the Flagellar Tip Complex

鞭毛尖端复合物的多肽

基本信息

  • 批准号:
    7140229
  • 负责人:
  • 金额:
    $ 15.61万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-09-01 至 2008-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Intraflagellar transport (IFT) is a process that is fundamental to the proper function of many cell types in the body, among them cells of the kidney where it is required for the assembly and maintenance of the primary cilia of the cells lining the nephron. Defects in the components of these primary cilia and defects in the machinery of IFT have been shown to cause polycystic kidney disease. The long term goals of this new project are to identify and characterize proteins of the flagellar tip complex and learn how they are involved in controlling particle movement during IFT. Why direct these studies to the flagellar tip? The microtubules (MTs) of the flagellar axoneme assemble and continuously turn over at the flagellar tip. The supply to and removal from the flagella of IFT components requires two motors: the MT-based motor protein kinesin-ll moves cargo from the base to the tip, and cytoplasmic dynein 1b moves cargo from the tip back to the base. Important activities relevant to the proper functioning of IFT occur at the flagellar tip, and these include MT assembly and disassembly, motor protein regulation, and cargo loading and unloading. Because an abrupt change in the direction of particle movement occurs only at the flagellar tip, the motor proteins must be regulated at the tip. Kinesin must be down regulated or turned off, and cytoplasmic dynein must be upregulated or turned on. The mechanisms used to control motor protein regulation and cargo unloading at the tip are unknown, but it is likely that a complex of proteins restricted to the flagellar tip, herein referred to as the flagellar tip complex (FTC), plays a definitive role in these processes. To test this hypothesis, three aims are proposed here: Having identified a polypeptide, CrEB1, that is localized at the flagellar tip. I will use rEB1 as a hook to fish out and identify other FTC proteins that are specific to the flagellar tip. The second aim will employ different approaches to identify structural and enzymatic components of the FTC that do not depend on an interaction with CrEBl. The third aim will characterize the FTC proteins identified via the first two aims and determine their function in IFT. Understanding more about the process of IFT is very important, as recent studies have shown that IFT defects cause polycystic kidney disease specifically, and defects in primary cilia are associated with a range of human disorders in addition to cystic diseases of the kidney, including retinal degeneration, obesity, hypertension, and diabetes, etc.
描述(申请人提供):鞭毛内转运(IFT)是体内许多细胞类型的正常功能的基本过程,其中肾脏细胞是组装和维持肾单位内细胞的初级纤毛所必需的。这些初级纤毛成分的缺陷和IFT机械的缺陷被证明是导致多囊肾病的原因。这一新项目的长期目标是识别和表征鞭毛尖端复合体的蛋白质,并了解它们如何参与控制IFT期间的颗粒运动。为什么要把这些研究指向鞭毛尖端呢?鞭毛轴丝的微管在鞭毛顶端组装并连续翻转。IFT组件的鞭毛供应和从鞭毛移除需要两个马达:基于MT的马达蛋白kinesin-11将货物从底部移动到末端,细胞质动力蛋白1b将货物从末端移动回基地。 与IFT的正常功能相关的重要活动发生在鞭毛顶端,包括MT组装和拆解、马达蛋白调节和货物装卸。由于颗粒运动方向的突变只发生在鞭毛顶端,因此马达蛋白必须在鞭毛顶端进行调节。激动素必须下调或关闭,细胞质动力蛋白必须上调或打开。用于控制马达蛋白调节和顶端卸货的机制尚不清楚,但很可能是限制在鞭毛顶端的蛋白质复合体,这里称为鞭毛顶端复合体(FTC),在这些过程中起着决定性的作用。为了验证这一假设,这里提出了三个目标:确定了一种定位于鞭毛顶端的多肽CREB1。我将使用Reb1作为一个钩子来钓鱼并鉴定其他针对鞭毛尖端的FTC蛋白。第二个目标将使用不同的方法来确定FTC的结构和酶成分,这些成分不依赖于与CrEB1的相互作用。第三个目标将鉴定通过前两个目标确定的FTC蛋白,并确定它们在IFT中的功能。更多地了解IFT的过程是非常重要的,因为最近的研究表明,IFT缺陷可以特异性地导致多囊肾病,而初级纤毛缺陷除了与肾脏的囊性疾病有关外,还与一系列人类疾病有关,包括视网膜变性、肥胖、高血压和糖尿病等。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A protein methylation pathway in Chlamydomonas flagella is active during flagellar resorption.
  • DOI:
    10.1091/mbc.e08-05-0470
  • 发表时间:
    2008-10
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Mark J. Schneider;Megan M Ulland;R. Sloboda
  • 通讯作者:
    Mark J. Schneider;Megan M Ulland;R. Sloboda
Protein methylation in full length Chlamydomonas flagella.
  • DOI:
    10.1002/cm.20387
  • 发表时间:
    2009-08
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sloboda, Roger D.;Howard, Louisa
  • 通讯作者:
    Howard, Louisa
Purification and localization of intraflagellar transport particles and polypeptides.
  • DOI:
    10.1007/978-1-60761-376-3_11
  • 发表时间:
    2009
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R. Sloboda
  • 通讯作者:
    R. Sloboda
Posttranslational protein modifications in cilia and flagella.
  • DOI:
    10.1016/s0091-679x(08)94018-8
  • 发表时间:
    2009
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R. Sloboda
  • 通讯作者:
    R. Sloboda
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ROGER D SLOBODA其他文献

ROGER D SLOBODA的其他文献

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{{ truncateString('ROGER D SLOBODA', 18)}}的其他基金

Dartmouth Rural STEM Educator Partnership
达特茅斯乡村 STEM 教育者合作伙伴关系
  • 批准号:
    10415182
  • 财政年份:
    2019
  • 资助金额:
    $ 15.61万
  • 项目类别:
Dartmouth Rural STEM Educator Partnership
达特茅斯乡村 STEM 教育者合作伙伴关系
  • 批准号:
    9973252
  • 财政年份:
    2019
  • 资助金额:
    $ 15.61万
  • 项目类别:
Dartmouth Rural STEM Educator Partnership
达特茅斯乡村 STEM 教育者合作伙伴关系
  • 批准号:
    10666522
  • 财政年份:
    2019
  • 资助金额:
    $ 15.61万
  • 项目类别:
Polypeptides of the Flagellar Tip Complex
鞭毛尖端复合物的多肽
  • 批准号:
    6956486
  • 财政年份:
    2005
  • 资助金额:
    $ 15.61万
  • 项目类别:
CALCIUM, PROTEIN PHOSPHORYLATION, AND CELL CYCLE CONTROL
钙、蛋白质磷酸化和细胞周期控制
  • 批准号:
    3303136
  • 财政年份:
    1990
  • 资助金额:
    $ 15.61万
  • 项目类别:
CALCIUM, PROTEIN PHOSPHORYLATION, AND CELL CYCLE CONTROL
钙、蛋白质磷酸化和细胞周期控制
  • 批准号:
    3303135
  • 财政年份:
    1990
  • 资助金额:
    $ 15.61万
  • 项目类别:
CALCIUM, PROTEIN PHOSPHORYLATION, AND CELL CYCLE CONTROL
钙、蛋白质磷酸化和细胞周期控制
  • 批准号:
    3303133
  • 财政年份:
    1990
  • 资助金额:
    $ 15.61万
  • 项目类别:
ANALYSIS OF FAST AXONAL TRANSPORT
快速轴突运输的分析
  • 批准号:
    3400107
  • 财政年份:
    1983
  • 资助金额:
    $ 15.61万
  • 项目类别:

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