Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics
Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics
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DOI：
10.15252/embj.201797741
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发表时间：
2018-07-02
期刊：
影响因子：
11.4
通讯作者：
Haglund, Kaisa
中科院分区：
文献类型：
--
作者：
Malerod, Lene;Le Borgne, Roland;Haglund, Kaisa
有丝分裂纺锤体（MS）的方向受到严格调控，但其分子机制尚未完全了解。在这里，我们报告了一个新的多功能衔接蛋白ALG-2相互作用蛋白X（阿利克斯）在调节MS方向除了其在胞质分裂中的作用。我们发现，阿利克斯被招募到中心体的中心粒周围物质（PCM），并促进不对称分裂的果蝇干细胞和上皮细胞，以及对称分裂的果蝇和人类上皮细胞中MS的正确取向。ALIX剥夺的细胞显示星形微管（MT）的形成缺陷，这导致MS取向异常。具体地说，阿利克斯通过果蝇纺锤体缺陷2（DSpd-2）/Cep 192招募到PCM，其中阿利克斯促进微管蛋白的积累，从而促进星形MT的有效成核。此外，阿利克斯通过募集微管相关蛋白1 S（MAP 1 S）来促进MT稳定性，该蛋白1 S稳定新形成的MT。总之，我们的研究结果表明，阿利克斯在提供稳健的MS的方向，通过促进星形MT形成在不对称和对称的细胞分裂过程中的一种新的进化保守的作用。
The orientation of the mitotic spindle (MS) is tightly regulated, but the molecular mechanisms are incompletely understood. Here we report a novel role for the multifunctional adaptor protein ALG-2-interacting protein X (ALIX) in regulating MS orientation in addition to its well-established role in cytokinesis. We show that ALIX is recruited to the pericentriolar material (PCM) of the centrosomes and promotes correct orientation of the MS in asymmetrically dividing Drosophila stem cells and epithelial cells, and symmetrically dividing Drosophila and human epithelial cells. ALIX-deprived cells display defective formation of astral microtubules (MTs), which results in abnormal MS orientation. Specifically, ALIX is recruited to the PCM via Drosophila Spindle defective 2 (DSpd-2)/Cep192, where ALIX promotes accumulation of-tubulin and thus facilitates efficient nucleation of astral MTs. In addition, ALIX promotes MT stability by recruiting microtubule-associated protein 1S (MAP1S), which stabilizes newly formed MTs. Altogether, our results demonstrate a novel evolutionarily conserved role of ALIX in providing robustness to the orientation of the MS by promoting astral MT formation during asymmetric and symmetric cell division.