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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Official URL: https://elifesciences.org/articles/61170

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 title	Project leader	Project code	Project type
A new class of microtubules in the spindle exerting forces on kinetochores-NewSpindleForce	Iva Tolić	647077	EK
Molecular origins of aneuploidies in healthy and diseased human tissues-ANEUPLOIDY	Iva Tolić; Nenad Pavin	855158	EK
Oscilatorna dinamika citoskeleta-OSCITON	Iva Tolić	IP-2014-09-4753	HRZZ
Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri-QuantiXLie	Hrvoje Buljan; Pavle Pandžić	KK.01.1.1.01.0004	EK