The microtubule-severing protein UNC-45A preferentially binds to curved microtubules and counteracts the microtubule-straightening effects of Taxol.
The microtubule-severing protein UNC-45A preferentially binds to curved microtubules and counteracts the microtubule-straightening effects of Taxol.
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DOI：
10.1016/j.jbc.2023.105355
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发表时间：
2023-11
影响因子：
4.8
通讯作者：
Bazzaro, Martina
中科院分区：
文献类型：
--
作者：
Hoshino, Asumi;Clemente, Valentino;Shetty, Mihir;Castle, Brian;Odde, David;Bazzaro, Martina
UNC-45A （UNC-45A）是目前已知的唯一一种与atp无关的微管切断蛋白。因此，它通过一种新的机制来切断mt。在体外和细胞中，unc - 45a介导的MT切断之前会出现MT弯曲。虽然mt是坚硬的生物聚合物，但在细胞中，它们经常弯曲，这种弯曲的结果可能会断裂。MT切割蛋白对MT晶格曲率的贡献在很大程度上是不确定的。通过体外生物物理重构和全内部荧光显微镜分析，我们发现UNC-45A在mt弯曲的区域富集，而在mt笔直的区域富集。在细胞中，我们发现UNC-45A过表达会增加MT曲率，而其缺失会产生相反的效果。我们还表明，这种效应的发生与肌动球蛋白的收缩性无关。最后，我们首次表明，在细胞中，紫杉醇使mt变直，而UNC-45A可以抵消药物的mt变直作用。
Uncoordinated protein 45A (UNC-45A) is the only known ATP-independent microtubule (MT)-severing protein. Thus, it severs MTs via a novel mechanism. In vitro and in cells, UNC-45A–mediated MT severing is preceded by the appearance of MT bends. While MTs are stiff biological polymers, in cells, they often curve, and the result of this curving can be breaking off. The contribution of MT-severing proteins on MT lattice curvature is largely undefined. Here, we show that UNC-45A curves MTs. Using in vitro biophysical reconstitution and total internal fluorescence microscopy analysis, we show that UNC-45A is enriched in the areas where MTs are curved versus the areas where MTs are straight. In cells, we show that UNC-45A overexpression increases MT curvature and its depletion has the opposite effect. We also show that this effect occurs is independent of actomyosin contractility. Lastly, we show for the first time that in cells, Paclitaxel straightens MTs, and that UNC-45A can counteracts the MT-straightening effects of the drug.
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影响因子：
11.8
作者：
Goldblum RR;McClellan M;White K;Gonzalez SJ;Thompson BR;Vang HX;Cohen H;Higgins L;Markowski TW;Yang TY;Metzger JM;Gardner MK
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影响因子：
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通讯作者：
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影响因子：
64.5
作者：
Alushin GM;Lander GC;Kellogg EH;Zhang R;Baker D;Nogales E
通讯作者：
Nogales E
影响因子：
6
作者：
Clemente V;Hoshino A;Meints J;Shetty M;Starr T;Lee M;Bazzaro M
通讯作者：
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