XMAP215 promotes microtubule catastrophe by disrupting the growing microtubule end.
XMAP215 promotes microtubule catastrophe by disrupting the growing microtubule end.
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DOI：
10.1083/jcb.202012144
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发表时间：
2021-10-04
期刊：
影响因子：
--
通讯作者：
Zanic M
中科院分区：
文献类型：
--
作者：
Farmer V;Arpağ G;Hall SL;Zanic M
快速生长的微管与大的保护性gtp帽有关，这就提出了细胞如何同时实现快速和高度动态的微管生长的问题。Farmer等人的研究表明，聚合酶XMAP215干扰生长中的微管末端，促进微管突变，尽管同时加速了微管的生长速度。gtp -微管蛋白帽被广泛接受用于保护微管免受灾难。gtp帽的大小被认为随着微管生长速率的增加而增加，这可能使快速生长的微管具有更高的稳定性。目前尚不清楚GTP-cap的什么特性允许尽管快速生长但频繁发生微管灾难。在这里，我们研究了在存在和不存在聚合酶XMAP215的情况下微管的生长。使用EB1作为GTP-cap标记，我们发现无论通过增加微管蛋白浓度还是通过XMAP215实现生长加速，GTP-cap大小都会增加。尽管平均GTP-cap大小增加，但与使用更多微管蛋白生长的微管相比，使用XMAP215生长的微管显示出更高的突变频率，而微管中的微管则不会发生突变。然而，与XMAP215聚合的微管生长速率波动较大；显示锥形和卷曲的末端；并以更快的生长速率和更高的EB1末端定位发生突变。我们的研究结果表明，XMAP215诱导的结构扰动超越了GTP-cap的保护作用，最终导致了微管灾难。
Fast-growing microtubules are associated with large protective GTP-caps, raising the question of how cells achieve simultaneously fast and highly dynamic microtubule growth. Farmer et al. show that polymerase XMAP215 perturbs the growing microtubule end to promote microtubule catastrophe, despite simultaneously accelerating the microtubule growth rate. The GTP-tubulin cap is widely accepted to protect microtubules against catastrophe. The GTP-cap size is thought to increase with the microtubule growth rate, presumably endowing fast-growing microtubules with enhanced stability. It is unknown what GTP-cap properties permit frequent microtubule catastrophe despite fast growth. Here, we investigate microtubules growing in the presence and absence of the polymerase XMAP215. Using EB1 as a GTP-cap marker, we find that GTP-cap size increases regardless of whether growth acceleration is achieved by increasing tubulin concentration or by XMAP215. Despite increased mean GTP-cap size, microtubules grown with XMAP215 display increased catastrophe frequency, in contrast to microtubules grown with more tubulin, for which catastrophe is abolished. However, microtubules polymerized with XMAP215 have large fluctuations in growth rate; display tapered and curled ends; and undergo catastrophe at faster growth rates and with higher EB1 end-localization. Our results suggest that structural perturbations induced by XMAP215 override the protective effects of the GTP-cap, ultimately driving microtubule catastrophe.
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DOI：
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发表时间：
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期刊：
The Journal of cell biology
影响因子：
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通讯作者：
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