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Optogenetic control of kinetochore function
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2017-08-14 00:00:00 , DOI: 10.1038/nchembio.2456
Huaiying Zhang 1 , Chanat Aonbangkhen 2 , Ekaterina V Tarasovetc 1 , Edward R Ballister 1 , David M Chenoweth 2 , Michael A Lampson 1
Affiliation  

Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools that can manipulate kinetochores on biologically relevant temporal and spatial scales. Optogenetic approaches have the potential to provide temporal and spatial control with molecular specificity. Here we report new chemical inducers of protein dimerization that allow us to both recruit proteins to and release them from kinetochores using light. We use these dimerizers to manipulate checkpoint signaling and molecular motor activity. Our findings demonstrate specialized properties of the CENP-E (kinesin-7) motor for directional chromosome transport to the spindle equator and for maintenance of metaphase alignment. This work establishes a foundation for optogenetic control of kinetochore function, which is broadly applicable to experimental probing of other dynamic cellular processes.

中文翻译:


着丝粒功能的光遗传学控制



着丝粒在细胞分裂过程中充当多种活动的中心,包括微管相互作用和纺锤体检查点信号传导。每个着丝粒都可以自主行动,并且当蛋白质被募集到着丝粒或从着丝粒中去除时,活性会迅速变化。了解这个动态系统需要能够在生物学相关的时间和空间尺度上操纵动粒的工具。光遗传学方法有潜力提供具有分子特异性的时间和空间控制。在这里,我们报告了蛋白质二聚化的新化学诱导剂,使我们能够利用光将蛋白质招募到动粒中并从动粒中释放它们。我们使用这些二聚体来操纵检查点信号传导和分子运动活动。我们的研究结果证明了 CENP-E (kinesin-7) 马达的特殊特性,用于将染色体定向运输到纺锤体赤道并维持中期排列。这项工作为动粒功能的光遗传学控制奠定了基础,广泛适用于其他动态细胞过程的实验探测。
更新日期:2017-09-08
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