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

Trupinić, Monika; Kokanović, Barbara; Ponjavić, Ivana; Barišić, Ivan; Šegvić, Siniša; Ivec, Arian; Tolić, Iva M. (2022) The chirality of the mitotic spindle provides a mechanical response to forces and depends on microtubule motors and augmin. Current Biology, 32 (11). 2480-2493e6. ISSN 0960-9822

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Abstract

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, which are 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 the spindle twist, we show that spindles are most chiral near the metaphase-to-anaphase transition. To assess the role of chirality in spindle mechanics, we compressed the spindles along their axis. This resulted in a 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. A 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 are more twisted than the elongated ones are, 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.

Item Type:	Article
Uncontrolled Keywords:	Mitotic spindle ; Mitosis ; Chirality ; Twist ; Torques ; Rotation ; Motor proteins ; Kinesins ; Augmin ; Spindle compression
Subjects:	NATURAL SCIENCES > Biology NATURAL SCIENCES > Interdisciplinary Natural Sciences
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Nova klasa mikrotubula u vretenu koja djeluje silama na kinetohore Tolić, Iva 647077 EK Ravnoteža sila i momenta sila u diobenom vretenu Pavin, Nenad IP-2019-04-5967 HRZZ Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomedicini Tolić, Iva Marija KK.01.1.1.04.0057 EK Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretena Tolić, Iva PZS-2019-02-7653 HRZZ Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivima Tolić, Iva; Pavin, Nenad 855158 EK
Depositing User:	Iva Tolić
Date Deposited:	04 Apr 2023 11:44
URI:	http://fulir.irb.hr/id/eprint/7842
DOI:	10.1016/j.cub.2022.04.035

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