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

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

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

Skup
Mitotic spindle: From living and synthetic systems to theory

Mjesto i datum
Split, Hrvatska, 28.03.2021. - 31.03.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Augmin ; Microtubules ; Nucleation

Sažetak
The mitotic spindle in human cells consists of microtubules 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 consequently the forces within the spindle. Here we show, by using siRNA depletion and CRISPR knock-out of the augmin complex subunits HAUS6 or HAUS8, that augmin is crucial for the nucleation of bridging microtubules, which laterally link sister kinetochore fibers. Its depletion reduced the number of microtubules within bridging fibers by around 80% and in kinetochore fibers by 40%, suggesting that the bridging microtubules are mainly nucleated at the surface of present microtubules. Moreover, the interkinetochore distance decreased preferentially for kinetochores that lack a bridging fiber, independently of the thickness of their k-fibers, implying that augmin affects forces on kinetochores largely via bridging fibers. Without augmin the number of bridging fibers decreased, with the remaining ones mostly confined to the spindle periphery with an increased overlap length. A slower poleward flux of microtubules after augmin depletion is indicative of slower sliding within the bridging fiber. 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

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