Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation
Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation
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DOI：
10.1038/nature14496
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发表时间：
2015-08-27
期刊：
影响因子：
64.8
通讯作者：
Baum, Buzz
中科院分区：
文献类型：
--
作者：
Rodrigues, Nelio T. L.;Lekomtsev, Sergey;Baum, Buzz
细胞分裂需要染色体分离和胞质分裂的精确协调。这种协调是通过在伸长的后期纺锤体(1)的中心向重叠的微管招募肌动蛋白调节因子ECT2来实现的。然后，ECT2向覆盖的皮质发出信号，促进分离染色体之间肌动球蛋白环的组装和收缩(1)。在这里，通过研究增殖的果蝇和人类细胞的分裂，我们证明了第二条平行的信号通路的存在，它触发了极细胞皮质在中期后期的松弛。这与皱纹形成、中心体和微管无关，而是依赖于PP1磷酸酶及其调节亚单位Sds22(参考文献2，3)。当分裂的染色体在中期向极皮层移动时，动粒定位的PP1-Sds22通过诱导Ezrin/Radioxin/moesin蛋白在细胞极点的去磷酸化和失活来帮助打破皮层对称性。这促进了皮层(2，3)的局部软化，促进了后期伸长和有序的细胞分裂。综上所述，这确定了一个保守的基于动粒的磷酸酶信号和底物，它们共同发挥功能，将后期染色体运动与皮质极化联系起来，从而将染色体分离与细胞分裂结合起来。
Cell division requires the precise coordination of chromosome segregation and cytokinesis. This coordination is achieved by the recruitment of an actomyosin regulator, Ect2, to overlapping microtubules at the centre of the elongating anaphase spindle(1). Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes(1). Here, by studying division in proliferating Drosophila and human cells, we demonstrate the existence of a second, parallel signalling pathway, which triggers the relaxation of the polar cell cortex at mid anaphase. This is independent of furrow formation, centrosomes and microtubules and, instead, depends on PP1 phosphatase and its regulatory subunit Sds22 (refs 2, 3). As separating chromosomes move towards the polar cortex at mid anaphase, kinetochore-localized PP1-Sds22 helps to break cortical symmetry by inducing the dephosphorylation and inactivation of ezrin/radixin/moesin proteins at cell poles. This promotes local softening of the cortex(2,3), facilitating anaphase elongation and orderly cell division. In summary, this identifies a conserved kinetochore-based phosphatase signal and substrate, which function together to link anaphase chromosome movements to cortical polarization, thereby coupling chromosome segregation to cell division.