The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement

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 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 (SAH) 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 respond to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.

Keywords: confinement; cytokinesis; mechanobiology; mitosis.