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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 , Chanat Aonbangkhen , Ekaterina V Tarasovetc , Edward R Ballister , David M Chenoweth , Michael A Lampson

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:

线粒体功能的光遗传控制

动植物作为细胞分裂过程中多种活动的枢纽,包括微管相互作用和纺锤体检查点信号传导。每个动粒都可以自主发挥作用,并且随着蛋白质被募集到动植物中或从动植物中去除,活动性会迅速变化。要了解这种动态系统,就需要能够在生物学上相关的时空尺度上操纵动臂的工具。光遗传学方法具有提供具有分子特异性的时空控制的潜力。在这里,我们报告了蛋白质二聚化的新化学诱导剂,它使我们既可以利用光将蛋白质募集到动植物,也可以将其从动植物中释放出来。我们使用这些二聚体来操纵检查点信号和分子运动活性。我们的研究结果表明CENP-E(驱动蛋白7)电机的特殊性质,用于将染色体定向转移到纺锤状赤道和维持中期对齐。这项工作为光动力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:2017-09-20
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