PLK1 plays dual roles in centralspindlin regulation during cytokinesis

Author:

Adriaans Ingrid E.12,Basant Angika3,Ponsioen Bas12,Glotzer Michael3ORCID,Lens Susanne M.A.12ORCID

Affiliation:

1. Oncode Institute, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

2. Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

3. Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL

Abstract

Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters centralspindlin onto the spindle midzone, making it unavailable for Aurora B at the equatorial cortex. We propose that PLK1 activity promotes the release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.

Funder

Netherlands Organization for Scientific Research

National Institutes of Health

Dutch Cancer Society

Publisher

Rockefeller University Press

Subject

Cell Biology

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