Phosphorylation controls spatial and temporal activities of motor-PRC1 complexes to complete mitosis
Phosphorylation controls spatial and temporal activities of motor-PRC1 complexes to complete mitosis
复制标题
磷酸化控制运动-PRC1复合物的空间和时间活动以完成有丝分裂
DOI：
10.1101/2023.03.11.531660
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gluszek-Kustusz A
中科院分区：
文献类型：
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作者：
Gluszek-Kustusz A
在有丝分裂过程中，纺锤体结构随着染色体分裂成子细胞而改变。胞质分裂1的微管交联蛋白调节剂（PRC1）对纺锤体稳定性、染色体分离和细胞质分裂的完成至关重要，但它如何将马达招募到中央纺锤体来协调染色体的分离尚不清楚。在这里，我们结合结构和细胞生物学的方法来证明人类的CENP‐E马达，这是染色体捕获和微管排列的必要条件，通过一个保守的疏水基序与PRC1结合。Kinesin‐4 Kif4A:PRC1也使用这种结合机制。通过体外重构，我们证明了CENP - E可以滑动反平行的PRC1交联微管。我们发现，CENP - E - PRC1相互作用的调控在空间和时间上与后期重叠微管的重新定位相耦合。最后，我们证明了prc1 -微管运动相互作用在后期控制染色体分裂，保持中央纺锤体完整性和确保细胞分裂是必不可少的。综上所述，我们的研究结果揭示了motor - PRC1复合物对染色体分离和细胞分裂耦合的细胞周期调控的分子基础。
During mitosis, spindle architecture alters as chromosomes segregate into daughter cells. The microtubule crosslinker protein regulator of cytokinesis 1 (PRC1) is essential for spindle stability, chromosome segregation and completion of cytokinesis, but how it recruits motors to the central spindle to coordinate the segregation of chromosomes is unknown. Here, we combine structural and cell biology approaches to show that the human CENP‐E motor, which is essential for chromosome capture and alignment by microtubules, binds to PRC1 through a conserved hydrophobic motif. This binding mechanism is also used by Kinesin‐4 Kif4A:PRC1. Usingin vitroreconstitution, we demonstrate that CENP‐E slides antiparallel PRC1‐crosslinked microtubules. We find that the regulation of CENP‐E ‐PRC1 interaction is spatially and temporally coupled with relocalization to overlapping microtubules in anaphase. Finally, we demonstrate that the PRC1–microtubule motor interaction is essential in anaphase to control chromosome partitioning, retain central spindle integrity and ensure cytokinesis. Taken together our findings reveal the molecular basis for the cell cycle regulation of motor‐PRC1 complexes to couple chromosome segregation and cytokinesis.