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Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces

Jagrić, Mihaela; Risteski, Patrik; Martinčić, Jelena; Milas, Ana; Tolić, Iva Marija (2021) Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces. eLife . ISSN 2050-084X

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Abstract

During metaphase, chromosome position at the spindle equator is regulated by the forces exerted by kinetochore microtubules and polar ejection forces. However, the role of forces arising from mechanical coupling of sister kinetochore fibers with bridging fibers in chromosome alignment is unknown. Here, we develop an optogenetic approach for acute removal of PRC1 to partially disassemble bridging fibers and show that they promote chromosome alignment. Tracking of the plus-end protein EB3 revealed longer antiparallel overlaps of bridging microtubules upon PRC1 removal, which was accompanied by misaligned and lagging kinetochores. Kif4A/kinesin-4 and Kif18A/kinesin-8 were found within the bridging fiber and largely lost upon PRC1 removal, suggesting that these proteins regulate the overlap length of bridging microtubules. We propose that PRC1-mediated crosslinking of bridging microtubules and recruitment of kinesins to the bridging fiber promote chromosome alignment by overlap length-dependent forces transmitted to the associated kinetochore fibers.

Item Type: Article
Uncontrolled Keywords: biology; biophysics; mitotic spindle; chromosome; optogenetics
Subjects: NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions: Division of Molecular Biology
Projects:
Project titleProject leaderProject codeProject type
A new class of microtubules in the spindle exerting forces on kinetochores-NewSpindleForceIva Tolić647077EK
Molecular origins of aneuploidies in healthy and diseased human tissues-ANEUPLOIDYIva Tolić; Nenad Pavin855158EK
Oscilatorna dinamika citoskeleta-OSCITONIva TolićIP-2014-09-4753HRZZ
Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri-QuantiXLieHrvoje Buljan; Pavle PandžićKK.01.1.1.01.0004EK
Depositing User: Maša Sabo
Date Deposited: 20 May 2021 13:09
Last Modified: 20 May 2021 13:09
URI: http://fulir.irb.hr/id/eprint/6398
DOI: 10.7554/eLife.61170

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