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Emergent properties of a mitotic Kif18b-MCAK-EB network
bioRxiv - Biochemistry Pub Date : 2020-08-10 , DOI: 10.1101/2020.08.09.242602
Toni McHugh , Julie P.I. Welburn

The precise regulation of microtubule length during mitosis is essential to assemble and position the mitotic spindle and segregate chromosomes. Prior work has identified key molecular players in this process, including the kinesin-18 Kif18b and the kinesin-13 Kif2C/MCAK, which both promote microtubule depolymerization. MCAK acts as a potent microtubule depolymerase diffusing short distances on microtubules, while Kif18b is a mitotic processive motor with weak depolymerase activity. However, the individual activities of these factors cannot explain the dramatic increase in microtubule dynamics in mitosis. Using in vitro reconstitution and single molecule imaging, we demonstrate that Kif18b, MCAK and the plus-end tracking protein EB3 act in an integrated manner to potently promote microtubule depolymerization. We find Kif18b acts as a microtubule plus end delivery factor for its cargo MCAK, and that Kif18b also promotes EB accumulation to plus ends independently of lattice nucleotide state. Together, our work defines the mechanistic basis for a cooperative Kif18b-EB-MCAK network with emergent properties that act to efficiently shorten microtubules in mitosis.

中文翻译:

有丝分裂Kif18b-MCAK-EB网络的新兴特性

有丝分裂期间微管长度的精确调节对于组装和定位有丝分裂纺锤体和分离染色体至关重要。先前的工作已经确定了该过程中的关键分子参与者,包括驱动微管解聚的驱动蛋白18 Kif18b和驱动蛋白13 Kif2C / MCAK。MCAK充当一种有效的微管解聚酶,可在微管上短距离扩散,而Kif18b是具有弱解聚酶活性的有丝分裂进行性运动。但是,这些因素的单独活动不能解释有丝分裂中微管动力学的急剧增加。使用体外重建和单分子成像,我们证明Kif18b,MCAK和正向追踪蛋白EB3以整合的方式起作用,以有效地促进微管解聚。我们发现Kif18b充当其货物MCAK的微管加上末端传递因子,并且Kif18b还能独立于晶格核苷酸状态而促进EB积累至末端。总之,我们的工作定义了具有新兴特性的协作Kif18b-EB-MCAK网络的机制基础,该特性可有效缩短有丝分裂中的微管。
更新日期:2020-08-11
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