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重构图揭示了鞭毛内运输的马达激活。

Reconstitution reveals motor activation for intraflagellar transport.

机构信息

Physik Department E22, Technische Universität München, Garching, Germany.

Munich Center for Integrated Protein Science, Munich, Germany.

出版信息

Nature. 2018 May;557(7705):387-391. doi: 10.1038/s41586-018-0105-3. Epub 2018 May 9.

DOI:10.1038/s41586-018-0105-3
PMID:29743676
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5967604/
Abstract

The human body represents a notable example of ciliary diversification. Extending from the surface of most cells, cilia accomplish a diverse set of tasks. Predictably, mutations in ciliary genes cause a wide range of human diseases such as male infertility and blindness. In Caenorhabditis elegans sensory cilia, this functional diversity appears to be traceable to the differential regulation of the kinesin-2-powered intraflagellar-transport (IFT) machinery. Here we reconstituted the first, to our knowledge, functional multi-component IFT complex that is deployed in the sensory cilia of C. elegans. Our bottom-up approach revealed the molecular basis of specific motor recruitment to the IFT trains. We identified the key component that incorporates homodimeric kinesin-2 into its physiologically relevant context, which in turn allosterically activates the motor for efficient transport. These results will enable the molecular delineation of IFT regulation, which has eluded understanding since its discovery more than two decades ago.

摘要

人体是纤毛多样化的一个显著例子。纤毛从大多数细胞表面延伸出来，完成了一系列多样化的任务。可以预见的是，纤毛基因的突变会导致一系列人类疾病，如男性不育和失明。在秀丽隐杆线虫的感觉纤毛中，这种功能多样性似乎可以追溯到驱动内鞭毛运输（IFT）的动力蛋白-2 的差异调节。在这里，我们重新构建了第一个，据我们所知，在秀丽隐杆线虫的感觉纤毛中部署的功能性多组件 IFT 复合物。我们的自下而上的方法揭示了特定马达招募到 IFT 列车的分子基础。我们确定了将同源二聚体动力蛋白-2纳入其生理相关环境的关键组件，进而变构激活了用于有效运输的马达。这些结果将使 IFT 调节的分子描述成为可能，自二十多年前发现以来，IFT 调节一直难以理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3da/5967604/8c43458e9ee4/emss-76863-f004.jpg
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EMBO Rep. 2017 Nov;18(11):1947-1956. doi: 10.15252/embr.201744097. Epub 2017 Sep 8.
2
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Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4714-E4723. doi: 10.1073/pnas.1619473114. Epub 2017 May 30.
3
Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery.
Nat Commun. 2025 Jan 26;16(1):1055. doi: 10.1038/s41467-025-56098-0.
4
Neurons dispose of hyperactive kinesin into glial cells for clearance.神经元将过度活跃的驱动蛋白排到神经胶质细胞中进行清除。
EMBO J. 2024 Jul;43(13):2606-2635. doi: 10.1038/s44318-024-00118-0. Epub 2024 May 28.
5
Mechanisms of Regulation in Intraflagellar Transport.鞭毛内运输的调控机制。
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6
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7
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