The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement

Cells sense and respond to forces from neighbouring cells and the extracellular matrix during growth and division. When cells undergo mitosis in a confined environment like in the tumour environment, high compressive stress causes unstable cell cortex and prolonged mitosis. Confined mitotic cells frequently experience chromosome loss and multipolar division. How the cortical instability affects cytokinesis under confinement is unclear. Here, we show that confined mitotic cells undergo furrow ingression comparable to unconfined mitotic cells but are strongly reliant on Aurora B kinase, a catalytic subunit of the chromosomal passenger complex (CPC) for its completion. Mechanistically, the cortical pool of CPC via the scaffolding protein INCENP sustains Aurora B at the equatorial cortex to drive furrow ingression under confinement. We identified mechanoresponsive elements within the single alpha-helix domain of INCENP that maintain the cortical CPC at the equatorial cortex to promote furrow ingression in response to high compressive stress. Thus, the cortical INCENP not only binds to actin filaments but also mechanically responds to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.

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Publication Details

Journal
Journal of Molecular Cell Biology
Published
2025-04-01
DOI
https://doi.org/10.1093/jmcb/mjaf019
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
0.00

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article

The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement

Jingjing Ding, Ting Gang Chew, M. Zhang, Junjie Wu et al.
Journal of Molecular Cell Biology
Microtubule and mitosis dynamics
article

The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement

Jingjing Ding, Ting Gang Chew, M. Zhang, Junjie Wu, Chao Wang, Bowen Chen, Chenxin Wang, Hui Yang
article en

Abstract

Cells sense and respond to forces from neighbouring cells and the extracellular matrix during growth and division. When cells undergo mitosis in a confined environment like in the tumour environment, high compressive stress causes unstable cell cortex and prolonged mitosis. Confined mitotic cells frequently experience chromosome loss and multipolar division. How the cortical instability affects cytokinesis under confinement is unclear. Here, we show that confined mitotic cells undergo furrow ingression comparable to unconfined mitotic cells but are strongly reliant on Aurora B kinase, a catalytic subunit of the chromosomal passenger complex (CPC) for its completion. Mechanistically, the cortical pool of CPC via the scaffolding protein INCENP sustains Aurora B at the equatorial cortex to drive furrow ingression under confinement. We identified mechanoresponsive elements within the single alpha-helix domain of INCENP that maintain the cortical CPC at the equatorial cortex to promote furrow ingression in response to high compressive stress. Thus, the cortical INCENP not only binds to actin filaments but also mechanically responds to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.

Journal of Molecular Cell BiologyVol. 17(4)
Second Affiliated Hospital of Zhejiang University (CN), Zhejiang University-University of Edinburgh Institute (CN), Zhejiang University of Technology (CN), University of Edinburgh (GB)
National Natural Science Foundation of China
Life in Land
Openalex Percentile: Top 81%
Microtubule and mitosis dynamics
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