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NuSAP 调节微管流和 Kif2A 定位，以确保染色体准确汇聚。

NuSAP regulates microtubule flux and Kif2A localization to ensure accurate chromosome congression.

机构信息

The Academy for Cell and Life Health, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

The Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.

出版信息

J Cell Biol. 2024 Feb 5;223(2). doi: 10.1083/jcb.202108070. Epub 2023 Dec 20.

DOI:10.1083/jcb.202108070
PMID:38117947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10733630/
Abstract

Precise chromosome congression and segregation requires the proper assembly of a steady-state metaphase spindle, which is dynamic and maintained by continuous microtubule flux. NuSAP is a microtubule-stabilizing and -bundling protein that promotes chromosome-dependent spindle assembly. However, its function in spindle dynamics remains unclear. Here, we demonstrate that NuSAP regulates the metaphase spindle length control. Mechanistically, NuSAP facilitates kinetochore capture and spindle assembly by promoting Eg5 binding to microtubules. It also prevents excessive microtubule depolymerization through interaction with Kif2A, which reduces Kif2A spindle-pole localization. NuSAP is phosphorylated by Aurora A at Ser-240 during mitosis, and this phosphorylation promotes its interaction with Kif2A on the spindle body and reduces its localization with the spindle poles, thus maintaining proper spindle microtubule flux. NuSAP knockout resulted in the formation of shorter spindles with faster microtubule flux and chromosome misalignment. Taken together, we uncover that NuSAP participates in spindle assembly, dynamics, and metaphase spindle length control through the regulation of microtubule flux and Kif2A localization.

摘要

精确的染色体着丝粒聚集和分离需要稳定的有丝分裂中期纺锤体的正确组装，而纺锤体是动态的，并通过持续的微管流来维持。NuSAP 是一种微管稳定和束状蛋白，可促进染色体依赖性纺锤体组装。然而，其在纺锤体动力学中的功能仍不清楚。在这里，我们证明 NuSAP 调节有丝分裂中期纺锤体长度的控制。在机制上，NuSAP 通过促进 Eg5 与微管结合，促进着丝粒捕获和纺锤体组装。它还通过与 Kif2A 相互作用防止微管过度解聚，从而减少 Kif2A 向纺锤体极的定位。NuSAP 在有丝分裂期间被 Aurora A 在丝氨酸 240 位磷酸化，这种磷酸化促进了它与纺锤体上的 Kif2A 的相互作用，并减少了它与纺锤体极的定位，从而保持适当的纺锤体微管流。NuSAP 敲除导致微管流更快和染色体错位的较短纺锤体的形成。总之，我们揭示了 NuSAP 通过调节微管流和 Kif2A 定位参与纺锤体组装、动力学和有丝分裂中期纺锤体长度的控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/6ad80fb97041/JCB_202108070_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/943fd576edd2/JCB_202108070_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/ee3e56766c39/JCB_202108070_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/285a02955a5d/JCB_202108070_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/668b4467f44d/JCB_202108070_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/0fcdb7319ea3/JCB_202108070_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/ecf4bd650a4e/JCB_202108070_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/2df1b148e6af/JCB_202108070_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/6ad80fb97041/JCB_202108070_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/943fd576edd2/JCB_202108070_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/ee3e56766c39/JCB_202108070_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/285a02955a5d/JCB_202108070_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/668b4467f44d/JCB_202108070_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/0fcdb7319ea3/JCB_202108070_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/ecf4bd650a4e/JCB_202108070_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/2df1b148e6af/JCB_202108070_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a554/10733630/6ad80fb97041/JCB_202108070_Fig5.jpg

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Mechanisms underlying spindle assembly and robustness.纺锤体组装和稳定性的机制。
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Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment.姊妹动粒纤维的长度依赖性向极通量促进染色体的排列。
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