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着丝粒组件是中心纺锤体组装所必需的。

Kinetochore components are required for central spindle assembly.

作者信息

Maton Gilliane, Edwards Frances, Lacroix Benjamin, Stefanutti Marine, Laband Kimberley, Lieury Tiffany, Kim Taekyung, Espeut Julien, Canman Julie C, Dumont Julien

机构信息

Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.

Ludwig Institute for Cancer Research/Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.

出版信息

Nat Cell Biol. 2015 May;17(5):697-705. doi: 10.1038/ncb3150. Epub 2015 Apr 13.

DOI:10.1038/ncb3150
PMID:25866924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4636119/
Abstract

A critical structure poised to coordinate chromosome segregation with division plane specification is the central spindle that forms between separating chromosomes after anaphase onset. The central spindle acts as a signalling centre that concentrates proteins essential for division plane specification and contractile ring constriction. However, the molecular mechanisms that control the initial stages of central spindle assembly remain elusive. Using Caenorhabditis elegans zygotes, we found that the microtubule-bundling protein SPD-1(PRC1) and the motor ZEN-4(MKLP-1) are required for proper central spindle structure during its elongation. In contrast, we found that the kinetochore controls the initiation of central spindle assembly. Specifically, central spindle microtubule assembly is dependent on kinetochore recruitment of the scaffold protein KNL-1, as well as downstream partners BUB-1, HCP-1/2(CENP-F) and CLS-2(CLASP); and is negatively regulated by kinetochore-associated protein phosphatase 1 activity. This in turn promotes central spindle localization of CLS-2(CLASP) and initial central spindle microtubule assembly through its microtubule polymerase activity. Together, our results reveal an unexpected role for a conserved kinetochore protein network in coupling two critical events of cell division: chromosome segregation and cytokinesis.

摘要

一个有望协调染色体分离与分裂平面确定的关键结构是后期开始后在分离的染色体之间形成的中央纺锤体。中央纺锤体作为一个信号中心，聚集了对分裂平面确定和收缩环收缩至关重要的蛋白质。然而，控制中央纺锤体组装初始阶段的分子机制仍然不清楚。利用秀丽隐杆线虫受精卵，我们发现微管成束蛋白SPD-1（PRC1）和动力蛋白ZEN-4（MKLP-1）在中央纺锤体伸长过程中对其正常结构是必需的。相比之下，我们发现动粒控制中央纺锤体组装的起始。具体而言，中央纺锤体微管组装依赖于支架蛋白KNL-1以及下游伙伴BUB-1、HCP-1/2（CENP-F）和CLS-2（CLASP）在动粒上的募集；并且受到动粒相关蛋白磷酸酶1活性的负调控。这反过来通过其微管聚合酶活性促进CLS-2（CLASP）在中央纺锤体上的定位和中央纺锤体微管的初始组装。总之，我们的结果揭示了一个保守的动粒蛋白网络在耦合细胞分裂的两个关键事件：染色体分离和胞质分裂中发挥的意想不到的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/89c2ab433833/nihms733822f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/a5b450516b38/nihms733822f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/5cc62dd10044/nihms733822f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/c6989f3b1757/nihms733822f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/d0e6a98bc672/nihms733822f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/89c2ab433833/nihms733822f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/a5b450516b38/nihms733822f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/5cc62dd10044/nihms733822f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/c6989f3b1757/nihms733822f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/d0e6a98bc672/nihms733822f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0599/4636119/89c2ab433833/nihms733822f5.jpg

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J Cell Biol. 2014 May 26;205(4):555-71. doi: 10.1083/jcb.201310018.
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A Bub1-Mad1 interaction targets the Mad1-Mad2 complex to unattached kinetochores to initiate the spindle checkpoint.Bub1-Mad1 相互作用将 Mad1-Mad2 复合物靶向未连接的动粒，以启动纺锤体检查点。
斯特龙姆综合征患者中包括大片段基因内缺失的 基因新的功能丧失性变异。
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An unconventional TOG domain is required for CLASP localization.非典型的 TOG 结构域对于 CLASP 的定位是必需的。
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Lateral and longitudinal compaction of PRC1 overlap zones drives stabilization of interzonal microtubules.PRC1 重叠区的侧向和纵向压实驱动了区际微管的稳定。
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Kinetochore component function in C. elegans oocytes revealed by 4D tracking of holocentric chromosomes.利用整体染色体的 4D 追踪揭示线虫卵母细胞中的着丝粒组件功能。
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