瑞士日内瓦大学生物化学系Emmanuel Derivery和Marcos Gonzalez Gaitan研究组合作发现，伸长复合体稳定微管以控制中枢纺锤体不对称和细胞命运决定因素的极化运输。该研究于2022年10月27日发表于国际一流学术期刊《自然—细胞生物学》杂志上。

他们确定了伸长复合体——一种参与蛋白质翻译保真度的蛋白质乙酰化酶和tRNA甲基化酶——的兼职功能是中枢纺锤体不对称的关键因素。伸长复合物通过稳定中心纺锤前侧的微管来控制纺锤不对称。因此，使用纳米体降低前侧伸长复合体的活性会使核内体误靶向到错误的细胞。在分子水平上，伸长复合体调节微管动力学独立于其乙酰化和甲基化酶活性。相反，伸长复合体直接与微管结合，提高聚合速度，同时降低突变频率。他们的数据建立了伸长复合体在细胞骨架极性和非对称信号传导核心中的非典型作用。

据介绍，不对称的细胞分裂产生两个子细胞，它们继承不同的决定因子，从而获得不同的命运。包含命运决定因素的核内体的极化运输最近成为不对称细胞分裂的进化保守特征，以增强蝇、鱼和哺乳动物的不对称细胞命运决定的鲁棒性。特别是，不对称的中枢纺锤体对信号核内体的极化分选有助于黑腹果蝇的不对称细胞分裂。然而，中枢纺锤体不对称是如何产生的仍不清楚。

附：英文原文

Title: Elongator stabilizes microtubules to control central spindle asymmetry and polarized trafficking of cell fate determinants

Author: Planelles-Herrero, Vicente Jose, Bittleston, Alice, Seum, Carole, Gaitan, Marcos Gonzalez, Derivery, Emmanuel

Issue&Volume: 2022-10-27

Abstract: Asymmetric cell division gives rise to two daughter cells that inherit different determinants, thereby acquiring different fates. Polarized trafficking of endosomes containing fate determinants recently emerged as an evolutionarily conserved feature of asymmetric cell division to enhance the robustness of asymmetric cell fate determination in flies, fish and mammals. In particular, polarized sorting of signalling endosomes by an asymmetric central spindle contributes to asymmetric cell division in Drosophila melanogaster. However, how central spindle asymmetry arises remains elusive. Here we identify a moonlighting function of the Elongator complex—an established protein acetylase and tRNA methylase involved in the fidelity of protein translation—as a key factor for central spindle asymmetry. Elongator controls spindle asymmetry by stabilizing microtubules differentially on the anterior side of the central spindle. Accordingly, lowering the activity of Elongator on the anterior side using nanobodies mistargets endosomes to the wrong cell. Molecularly, Elongator regulates microtubule dynamics independently of its acetylation and methylation enzymatic activities. Instead, Elongator directly binds to microtubules and increases their polymerization speed while decreasing their catastrophe frequency. Our data establish a non-canonical role of Elongator at the core of cytoskeleton polarity and asymmetric signalling.

DOI: 10.1038/s41556-022-01020-9

Source: https://www.nature.com/articles/s41556-022-01020-9