Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA 94158, USA; Developmental & Stem Cell Biology Graduate Program, UCSF, San Francisco, CA 94143, USA.
Department of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA 94158, USA; Tetrad Graduate Program, UCSF, San Francisco, CA 94158, USA.
Dev Cell. 2021 Nov 8;56(21):3006-3018.e5. doi: 10.1016/j.devcel.2021.09.011. Epub 2021 Oct 5.
At each cell division, the spindle self-organizes from microtubules and motors. In human spindles, the motors dynein and Eg5 generate contractile and extensile stress, respectively. Inhibiting dynein or its targeting factor NuMA leads to unfocused, turbulent spindles, and inhibiting Eg5 leads to monopoles; yet, bipolar spindles form when both are inhibited together. What, then, are the roles of these opposing motors? Here, we generate NuMA/dynein- and Eg5-doubly inhibited spindles that not only attain a typical metaphase shape and size but also undergo anaphase. However, these spindles have reduced microtubule dynamics and are mechanically fragile, fracturing under force. Furthermore, they exhibit lagging chromosomes and a dramatic left-handed twist at anaphase. Thus, although these opposing motors are not required for spindle shape, they are essential to its mechanical and functional robustness. This work suggests a design principle whereby opposing active stresses provide robustness to force-generating cellular structures.
在每个细胞分裂过程中，纺锤体自组装形成微管和马达。在人类纺锤体中，马达 dynein 和 Eg5 分别产生收缩力和延伸力。抑制 dynein 或其靶向因子 NuMA 会导致纺锤体失去焦点、不稳定，而抑制 Eg5 会导致单极体；然而，当两者同时被抑制时，会形成双极纺锤体。那么，这些相反的马达的作用是什么呢？在这里，我们生成了 NuMA/dynein 和 Eg5 双重抑制的纺锤体，这些纺锤体不仅具有典型的中期形状和大小，而且还能进行后期。然而，这些纺锤体的微管动力学降低，机械脆弱，在受力下会断裂。此外，它们在后期表现出滞后染色体和明显的左手扭曲。因此，尽管这些相反的马达不是纺锤体形状所必需的，但它们对于纺锤体的机械和功能稳健性是必不可少的。这项工作提出了一个设计原则，即相反的主动应力为产生力的细胞结构提供稳健性。
