WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin.
WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin.
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WDR62 作为 TPX2/Aurora A 和剑蛋白之间的衔接蛋白调节纺锤体动力学
DOI：
10.1083/jcb.202007167
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发表时间：
2021-08-02
期刊：
影响因子：
--
通讯作者：
Jiang K
中科院分区：
文献类型：
--
作者：
Huang J;Liang Z;Guan C;Hua S;Jiang K
Huang等人揭示了小头相关蛋白WDR 62对弯曲的微管具有内在的亲和力，并通过充当其招募因子TPX 2/Aurora A和效应器katanin之间的衔接蛋白来调节纺锤体动力学。WDR 62是一种微管相关蛋白，定位于纺锤体极点，调节纺锤体组织，但其机制尚不清楚。在这里，我们表明，WDR 62调节纺锤体动力学招募katanin的纺锤体极，并进一步揭示了TPX 2-极光A-WDR 62-katanin轴细胞。通过结合细胞和体外实验，我们证明，WDR 62显示出对动态GDP-MT的弯曲段以及GMPCPP和紫杉醇稳定的MT的偏好，这表明它识别扩展的MT晶格。与该性质一致，单独的WDR 62在将卡他宁募集到GDP-MT中是无效的，而与TPX 2/Aurora A复合的WDR 62可以在体外有效地促进卡他宁介导的GDP-MT的切断。此外，MT结合亲和力的WDR 62是通过JNK磷酸化诱导的分子内相互作用的自抑制。我们建议，WDR 62是一个非典型的MAP和功能之间的衔接蛋白的招募因子TPX 2/极光A和效应katanin编排的纺锤体动力学的调节。
Huang et al. reveal that the microcephaly-related protein WDR62 possesses an intrinsic affinity for curved microtubules and regulates spindle dynamics by functioning as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin. WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2–Aurora A–WDR62–katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics.
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影响因子：
3.7
作者：
Eckert T;Le DT;Link S;Friedmann L;Woehlke G
通讯作者：
Woehlke G
人类TPX2是将极光-A激酶靶向纺锤体所必需的。
影响因子：
7.8
作者：
Kufer, Thomas A;Sillje, Herman H W;Korner, Roman;Gruss, Oliver J;Meraldi, Patrick;Nigg, Erich A
通讯作者：
Nigg, Erich A
影响因子：
7.7
作者：
Kodani A;Yu TW;Johnson JR;Jayaraman D;Johnson TL;Al-Gazali L;Sztriha L;Partlow JN;Kim H;Krup AL;Dammermann A;Krogan NJ;Walsh CA;Reiter JF
通讯作者：
Reiter JF
DOI：
10.1083/jcb.200301147
发表时间：
2003-06-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Janson ME;de Dood ME;Dogterom M
通讯作者：
Dogterom M
DOI：
10.1042/bj20110284
发表时间：
2011-11-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Cohen-Katsenelson K;Wasserman T;Khateb S;Whitmarsh AJ;Aronheim A
通讯作者：
Aronheim A