Coordinated control of both microtubule ends regulates mitotic spindle length

Fiorenza, Shane A.; Cheeran, Sheba; Doria, Elena; Tolić, Iva M.; Meraldi, Patrick; Pavin, Nenad (2026) Coordinated control of both microtubule ends regulates mitotic spindle length. Nature Communications . ISSN 2041-1723 (In Press)

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Abstract

The mitotic spindle is a biomechanical structure whose length must be precisely controlled to ensure faithful chromosome segregation. The treadmilling of microtubules towards spindle poles, termed poleward flux, is involved in spindle length control. However, poleward flux velocity has been shown to be both inversely and directly proportional to spindle length, a contradiction that remains unexplained by current mechanisms. Here we introduce a model which demonstrates that length-dependent regulation at both microtubule ends allows plus- and minus-end dynamics to synchronize with one another, enabling pathways of poleward-flux-based spindle length control which rectify previous results. Moreover, our model predicts that spindle length and poleward flux velocity can vary independently via simultaneous perturbations at both microtubule ends, which we validate with protein depletion experiments in human cells. Finally, we provide experimental evidence for length-dependent accumulation of proteins at microtubule minus-ends. Our results thus resolve a longstanding paradox and provide mechanistic insight into the reciprocal control of spindle length and poleward flux.

Item Type:	Article
Uncontrolled Keywords:	Mitotic spindle; Spindle length regulation; Microtubule dynamics; Poleward flux; Microtubule end coordination
Subjects:	NATURAL SCIENCES > Physics > Biophysics and Medical Physics NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molecular origins of aneuploidies in healthy and diseased human tissues - Aneuploidy Iva M. Tolić, N. Pavin 855158 ERC - SyG How centrosome age affects the formation, resolution, and fate of polar chromosomes - CentrPol Iva m. Tolić IPCH-2022-10-9344 HRZZ - IPCH Role of microtubule minus-end-binding proteins in orchestrating mitotic spindle geometry - ROMBOSpindle N. Pavin IP-2025-02-9880 HRZZ - IP Using first-principle modeling to study multipolar mitotic spindles in cancerous cells” – TRIPOLES Shane A. Fiorenza 101151485 MSCA
Depositing User:	Ivana Šarić
Date Deposited:	09 Nov 2026 12:25
URI:	https://fulir.irb.hr:/id/eprint/12192
DOI:	10.1038/s41467-026-78426-8

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