Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing
- University of Utah, United States
- University of Utah School of Medicine, United States
Abstract
The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop during an active checkpoint. ACBs are derived from Mitotic Interchromatin Granules (MIGs), transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed abscission and delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.
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Article and author information
Author details
Wesley I Sundquist
Katharine S Ullman
Funding
National Institutes of Health (NIH R01GM112080)
- Wesley I Sundquist
- Katharine S Ullman
Huntsman Cancer Foundation (CRR award)
- Wesley I Sundquist
- Katharine S Ullman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Strohacker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing
eLife 10:e63743.
https://doi.org/10.7554/eLife.63743
