The stoichiometry of the outer kinetochore is modulated by microtubule-proximal regulatory factors
The stoichiometry of the outer kinetochore is modulated by microtubule-proximal regulatory factors
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DOI：
10.1083/jcb.201810070
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发表时间：
2019-07-01
影响因子：
7.8
通讯作者：
Gerton, Jennifer L.
中科院分区：
文献类型：
--
作者：
Dhatchinamoorthy, Karthik;Unruh, Jay R.;Gerton, Jennifer L.
动粒是一个大的分子机器，它将染色体附着在微管上并促进染色体分离。动粒包括与着丝粒DNA相关的子模块和附着在微管上的子模块。在分裂后期增加了几个动粒子模块的额外拷贝，包括微管结合模块Ndc 80。虽然控制可塑性的因素尚不清楚，但它们可能包括基于微管-动粒相互作用的调节。我们报告说，Fin 1本地化的微管近端边缘的动粒集群在后期基于单粒子平均的超分辨率图像。组装正常级别的Dam 1和Ndc 80子模块需要Fin 1。Ndc 80的水平进一步取决于Dam 1微管结合复合物。我们的研究结果表明，外动粒子模块的化学计量受到强烈影响的因素在动粒微管接口，如Fin 1和Dam 1，和磷酸化的细胞周期蛋白依赖性激酶。外动粒化学计量是显着的塑料和响应微管近端调节。
The kinetochore is a large molecular machine that attaches chromosomes to microtubules and facilitates chromosome segregation. The kinetochore includes submodules that associate with the centromeric DNA and submodules that attach to microtubules. Additional copies of several submodules of the kinetochore are added during anaphase, including the microtubule binding module Ndc80. While the factors governing plasticity are not known, they could include regulation based on microtubule-kinetochore interactions. We report that Fin1 localizes to the microtubule-proximal edge of the kinetochore cluster during anaphase based on single-particle averaging of super-resolution images. Fin1 is required for the assembly of normal levels of Dam1 and Ndc80 submodules. Levels of Ndc80 further depend on the Dam1 microtubule binding complex. Our results suggest the stoichiometry of outer kinetochore submodules is strongly influenced by factors at the kinetochore-microtubule interface such as Fin1 and Dam1, and phosphorylation by cyclin-dependent kinase. Outer kinetochore stoichiometry is remarkably plastic and responsive to microtubule-proximal regulation.