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Mms19 promotes spindle microtubule assembly in Drosophila neural stem cells
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-11-19 , DOI: 10.1371/journal.pgen.1008913
Rohan Chippalkatti 1, 2 , Boris Egger 3 , Beat Suter 1
Affiliation  

Mitotic divisions depend on the timely assembly and proper orientation of the mitotic spindle. Malfunctioning of these processes can considerably delay mitosis, thereby compromising tissue growth and homeostasis, and leading to chromosomal instability. Loss of functional Mms19 drastically affects the growth and development of mitotic tissues in Drosophila larvae and we now demonstrate that Mms19 is an important factor that promotes spindle and astral microtubule (MT) growth, and MT stability and bundling. Mms19 function is needed for the coordination of mitotic events and for the rapid progression through mitosis that is characteristic of neural stem cells. Surprisingly, Mms19 performs its mitotic activities through two different pathways. By stimulating the mitotic kinase cascade, it triggers the localization of the MT regulatory complex TACC/Msps (Transforming Acidic Coiled Coil/Minispindles, the homolog of human ch-TOG) to the centrosome. This activity of Mms19 can be rescued by stimulating the mitotic kinase cascade. However, other aspects of the Mms19 phenotypes cannot be rescued in this way, pointing to an additional mechanism of Mms19 action. We provide evidence that Mms19 binds directly to MTs and that this stimulates MT stability and bundling.



中文翻译:

Mms19促进果蝇神经干细胞纺锤体微管组装

有丝分裂取决于有丝分裂纺锤体的及时组装和正确方向。这些过程的故障会大大延迟有丝分裂,从而损害组织生长和体内平衡,并导致染色体不稳定。功能性Mms19的丧失极大地影响了果蝇幼虫有丝分裂组织的生长和发育,我们现在证明Mms19是促进纺锤体和星形微管(MT)生长以及 MT 稳定性和成束的重要因素。Mms19功能对于有丝分裂事件的协调以及神经干细胞特有的有丝分裂的快速进展是必需的。令人惊讶的是,Mms19通过两种不同的途径进行有丝分裂活动。通过刺激有丝分裂激酶级联,它触发 MT 调节复合物 TACC/Msps(转化酸性卷曲线圈/小纺锤体,人类 ch-TOG 的同源物)定位到中心体。Mms19 的这种活性可以通过刺激有丝分裂激酶级联来恢复。然而,Mms19表型的其他方面无法通过这种方式挽救,这表明Mms19作用的另一种机制。我们提供的证据表明 Mms19 直接与 MT 结合,这会刺激 MT 稳定性和捆绑。

更新日期:2020-11-21
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