HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2.
HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2.
复制标题
HURP 通过稳定微管并与 TPX2 协同作用来促进纺锤体组装。
DOI：
10.1101/2023.12.18.571906
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Petry,Sabine
中科院分区：
文献类型：
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作者：
Valdez,Venecia;Ma,Meisheng;Gouveia,Bernardo;Zhang,Rui;Petry,Sabine
在脊椎动物纺锤体中，大多数微管是通过分支微管成核形成的，由此微管沿着预先存在的微管的侧面成核。肝癌上调蛋白（HURP）是一种微管相关蛋白，与纺锤体组装有关，但其作用方式尚未确定。在这项研究中，我们表明，HURP是必需的RanGTP诱导的分支微管成核inXenopusegg提取物。具体而言，HURP稳定微管晶格以促进γ-TuRC形成微管。该功能通过增强对TPX 2缩合物的定位而转变为促进分支微管成核，TPX 2缩合物形成微管上分支位点的核心。最后，我们提供了一个高分辨率的cryo-EM结构的HURP的微管，揭示了如何HURP绑定稳定的微管晶格。我们提出了一个模型，其中HURP稳定微管在其形成过程中，和TPX 2优先富集HURP微管，以促进分支微管成核，从而纺锤体组装。
In vertebrate spindles, most microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation inXenopusegg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from γ-TuRC. This function is shifted to promote branching microtubule nucleation through enhanced localization to TPX2 condensates, which form the core of the branch site on microtubules. Lastly, we provide a high-resolution cryo-EM structure of HURP on the microtubule, revealing how HURP binding stabilizes the microtubule lattice. We propose a model in which HURP stabilizes microtubules during their formation, and TPX2 preferentially enriches HURP to microtubules to promote branching microtubule nucleation and thus spindle assembly.