Naslov
Augmin regulates kinetochore tension and spatial arrangement of spindle microtubules by nucleating bridging fibers

Autori
Koprivec, Isabella ; Štimac, Valentina ; Manenica, Martina ; Simunić, Juraj ; Tolić, Iva M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Cell Bio Virtual 2020 | An ASCB|EMBO Meeting

Mjesto i datum
Philadelphia (PA), Sjedinjene Američke Države, 02.12.2020. - 16.12.2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Augmin ; Microtubules ; Nucleation

Sažetak
The mitotic spindle functions as a molecular micromachine that evenly distributes chromosomes into two daughter cells during cell division. A major mechanical element of the spindle are kinetochore fibers attached to sister kinetochores on each chromosome and laterally linked by a bundle of antiparallel microtubules called the bridging fiber. Spindle microtubules are mainly nucleated at the centrosome and on the lateral surface of existing microtubules by the augmin complex. However, it is unknown how the augmin‐ mediated nucleation affects functionally distinct microtubule bundles and thus the architecture and forces within the spindle. Here we show, by using siRNA depletion and CRISPR knock‐out of the augmin complex subunits HAUS6 and HAUS8 in human cells, that augmin is a major contributor to the nucleation of bridging microtubules. Augmin depletion resulted in a ∼70% reduction of the microtubule number in bridging fibers and ∼40% in kinetochore fibers, suggesting that the bridging microtubules are largely nucleated at the surface of present microtubules. In augmin‐depleted cells, the interkinetochore distance decreases preferentially for kinetochores that lack a bridging fiber, independently of the thickness of their k‐fibers, indicating that augmin affects forces on kinetochores largely via bridging fibers. Without augmin the number of bridging fibers decreases, with the remaining ones mostly confined to the spindle periphery with an increased overlap length. The reduced number of microtubules also results in a slower poleward flux. Our results demonstrate a critical role of augmin in the formation of bridging microtubules and proper architecture of the metaphase spindle, suggesting a model where sliding of augmin‐ nucleated bridging microtubules promotes poleward flux of k‐fibers and thus tension on kinetochores.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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