Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment

Risteski, Patrik; Božan, Domagoj; Jagrić, Mihaela; Bosilj, Agneza; Pavin, Nenad; Tolić, Iva M. (2022) Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment. Cell Reports, 40 (5). ISSN 2211-1247

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Abstract

Chromosome alignment at the spindle equator promotes proper chromosome segregation and depends on pulling forces exerted at kinetochore fiber tips together with polar ejection forces. However, kinetochore fibers are also subjected to forces driving their poleward flux. Here we introduce a flux-driven centering model that relies on flux generated by forces within the overlaps of bridging and kinetochore fibers. This centering mechanism works so that the longer kinetochore fiber fluxes faster than the shorter one, moving the kinetochores toward the center. We develop speckle microscopy in human spindles and confirm the key prediction that kinetochore fiber flux is length dependent. Kinetochores are better centered when overlaps are shorter and the kinetochore fiber flux slower than the bridging fiber flux. We identify Kif18A and Kif4A as overlap and flux regulators and NuMA as a fiber coupler. Thus, length-dependent sliding forces exerted by the bridging fiber onto kinetochore fibers support chromosome alignment.

Item Type:	Article
Uncontrolled Keywords:	chromosome alignment ; mitotic spindle ; kinetochore ; microtubule poleward flux ; speckle microscopy ; mathematical model
Subjects:	NATURAL SCIENCES > Physics NATURAL SCIENCES > Biology NATURAL SCIENCES > Interdisciplinary Natural Sciences
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivima Tolić, Iva; Pavin, Nenad 855158 EK Nova klasa mikrotubula u vretenu koja djeluje silama na kinetohore Tolić, Iva 647077 EK Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretena Tolić, Iva PZS-2019-02-7653 HRZZ 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 Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri Buljan, Hrvoje; Pandžić, Pavle; Tuček, Vit; Marketin, Tomislav KK.01.1.1.01.0004 EK
Depositing User:	Patrik Risteski
Date Deposited:	05 Sep 2022 11:55
URI:	http://fulir.irb.hr/id/eprint/7546
DOI:	10.1016/j.celrep.2022.111169

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