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转录辅助因子CrEDF1调控纤毛长度平衡的分子机理

批准号:
32170702
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
胡长峰
依托单位:
学科分类:
细胞器及亚细胞结构、互作与功能
结题年份:
2025
批准年份:
2021
项目状态:
已结题
项目参与者:
邢俊俏、李璨、王震

项目摘要

结项摘要

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中文摘要
细胞怎样调控自身细胞器的大小是细胞生物学中一个重要的未解难题。真核生物纤毛或鞭毛是研究细胞器大小调控的理想模型,主要是由于纤毛的大小可由长度衡量。通过大规模突变体筛选得到衣藻纤毛长度不等长突变体edf1。研究表明纤毛组装过程中CrEDF1表达增加,CrEDF1蛋白进入纤毛依赖于纤毛内运输机制。CrEDF1也存在于细胞核中并以转录辅助因子的形式参与纤毛基因转录。研究还发现纤毛长度调控复合物LRC影响CrEDF1在纤毛和细胞核中的定位。拟进一步研究细胞周期过程中CrEDF1的表达,CrEDF1在纤毛和细胞核中的运输以及LRC调控CrEDF1定位等的分子机制。深入研究单细胞水平CrEDF1在纤毛长度平衡中的作用机制,及其靶基因调控纤毛组装和解聚的分子机理。研究CrEDF1调控纤毛长度平衡的作用机制,将有助于发现和理解其他细胞器大小调控的作用机理,从而促进细胞器大小控制研究领域的发展。
英文摘要
An important unanswered question in cell biology is how cells control the size of their organelles. Eukaryotic cilium or flagellum is an ideal model system to investigate the mechanism of organelle size control, mainly because the organelle maintains a constant diameter as it assembles and disassembles, thus making it essentially a one-dimensional organelle and its size can be determined simply by measuring its length. In the previous study, we obtained a distinct unequal-length cilia mutant edf1, by using large-scale insertional mutagenesis in Chlamydomonas which is a model organism for studies of cilia. Our results showed that the expression of CrEDF1 was up-regulated by deflagellation, and the transport of CrEDF1 into cilia during ciliary assembly depended on IFT. However, CrEDF1 also existed in the nucleus and regulated the transcription of cilia-associated genes as a transcriptional activator. In addition, the ciliary and nuclear localization of the CrEDF1 protein were lost when genes that made up the proteins in the cytoplasmic length regulatory complex (LRC) were mutated. Hence, our study aimed to further investigate the regulatory mechanisms of CrEDF1 expression during cell cycle, CrEDF1 transport in cilia and nuclei, and the LRC regulating the localization of CrEDF1. We intend to further study the mechanism by which CrEDF1 is participated in ciliary length equalization in single cells, and unravel the molecular mechanisms of CrEDF1 target genes involved in ciliary assembly and disassembly. The study on the molecular mechanism of transcriptional coactivator CrEDF1 in regulating ciliary length equalization will facilitate the discovery and.understanding of the mechanisms of other complex organelle size regulation, thus promoting the development of the field of organelle size control.
细胞怎样感知和调控自身细胞器大小是细胞生物学中最重要的未解难题之一。现阶段对细胞器大小调控的分子机制了解甚少,尤其是多拷贝细胞器大小平衡调控的机理,鲜有报道。莱茵衣藻细胞拥有等长的两根纤毛,其中一根纤毛切割分离后,会在断裂处重新再生长出新的纤毛,与此同时,另外一根纤毛则会发生解聚,等两根纤毛长度等长后再同时组装到正常长度,这种现象称之为“长-零响应”(Long-zero response)。虽然这一现象已经被发现50余年,但是其调控机制尚不清楚,项目研究证实转录辅助因子CrEDF1参与纤毛长度平衡调控过程。. 项目主要以莱茵衣藻为模式生物研究纤毛长度平衡调控的分子机制,通过高通量筛选获得纤毛长度缺陷突变体edf1,并对其纤毛相关性状进行了系统分析。项目阐明了CrEDF1进入纤毛和细胞核中的分子机制,确定了CrEDF1调控纤毛基因转录表达的分子机理,揭示了纤毛长度调控复合物LRC参与纤毛长度调控的机制,详细阐述了靶基因CrMLK1等介导的纤毛组装和解聚机制,系统建立了依赖于CrEDF1的纤毛长度平衡调控信号通路。项目揭示CrEDF1调控纤毛长度平衡的分子机理,开创了多纤毛细胞中纤毛长度平衡调控相关研究领域,为进一步揭示其他复杂多拷贝细胞器的大小平衡调控机制提供了新的研究思路。
转录辅助因子CrEDF1调控纤毛长度平衡的分子机理
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    58万元
  • 批准年份:
    2021
  • 负责人:
    胡长峰
  • 依托单位:
细胞核蛋白CrXAP5依赖的纤毛基因转录表达分子机制研究
  • 批准号:
    31601090
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    22.0万元
  • 批准年份:
    2016
  • 负责人:
    胡长峰
  • 依托单位:
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