Naslov
The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin

Autori
Trupinić, Monika ; Kokanović, Barbara ; Ponjavić, Ivana ; Ivec, Arian ; Tolić, Iva M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
EMBO / EMBL Symposium: Microtubules: From Atoms to Complex Systems

Mjesto i datum
Heidelberg, Njemačka, 08.06.2022. - 11.06.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Mitotic spindle ; Mitosis ; Chirality ; Twist ; Torques ; Rotation ; Motor proteins ; Kinesins ; Augmin ; Spindle compression

Sažetak
Forces produced by motor proteins and microtubule dynamics within the mitotic spindle are crucial for proper chromosome segregation. In addition to linear forces, rotational forces or torques are present in the spindle, reflected in the left- handed twisted shapes of microtubule bundles that make the spindle chiral. However, the biological role and molecular origins of spindle chirality are unknown. By developing methods for measuring spindle twist, we show that spindles are most chiral near the metaphase-to-anaphase transition. To assess the role of chirality in maintaining spindle robustness under force, we compressed the spindles along their axis. This resulted in stronger left-handed twist, suggesting that the twisted shape allows for a mechanical response to forces. Inhibition or depletion of motor proteins that perform chiral stepping, Eg5/kinesin-5, Kif18A/kinesin-8, MKLP1/kinesin-6, and dynein, decreased the left-handed twist or led to right-handed twist, implying that these motors regulate the twist by rotating microtubules within their antiparallel overlaps or at the spindle pole. Right-handed twist was also observed after the depletion of the microtubule nucleator augmin, indicating its contribution to the twist through the nucleation of antiparallel bridging microtubules. The uncovered switch from left- handed to right-handed twist reveals the existence of competing mechanisms that promote twisting in opposite directions. As round spindles were more twisted than elongated ones, we infer that bending and twisting moments are generated by similar molecular mechanisms and propose a physiological role for spindle chirality in allowing the spindle to absorb mechanical load.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA