Opposing motors provide mechanical and functional robustness in the human spindle
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 mon...
Gespeichert in:
Veröffentlicht in: | Developmental cell 2021-11, Vol.56 (21), p.3006-3018.e5 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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.
[Display omitted]
•Spindles lacking NuMA/dynein and Eg5 motor activities attain normal shape and size•Microtubule organization and flux are disrupted without these opposing motors•Spindles lacking NuMA/dynein and Eg5 are mechanically fragile in metaphase•Opposing forces are required to prevent twisting and segregation errors in anaphase
Successful cell division relies on the robust assembly of the microtubule-based spindle. Neahring et al. show that the opposing mitotic motors NuMA/dynein and Eg5 are not required for human spindle formation but are instead essential for its mechanical, structural, and functional robustness. |
---|---|
ISSN: | 1534-5807 1878-1551 |
DOI: | 10.1016/j.devcel.2021.09.011 |