Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing
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 regulato...
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doaj-a56c544995e947659cbf56d6a5b966f32021-09-13T15:43:15ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.63743Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timingLauren K Williams0https://orcid.org/0000-0001-9650-1042Douglas R Mackay1Madeline A Whitney2Genevieve C Couldwell3Wesley I Sundquist4https://orcid.org/0000-0001-9988-6021Katharine S Ullman5https://orcid.org/0000-0003-3693-2830Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United StatesDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United StatesDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United StatesDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, United StatesDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United StatesThe 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, 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.https://elifesciences.org/articles/63743abscissioncell divisionESCRT pathwaycytokinesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lauren K Williams Douglas R Mackay Madeline A Whitney Genevieve C Couldwell Wesley I Sundquist Katharine S Ullman |
spellingShingle |
Lauren K Williams Douglas R Mackay Madeline A Whitney Genevieve C Couldwell Wesley I Sundquist Katharine S Ullman Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing eLife abscission cell division ESCRT pathway cytokinesis |
author_facet |
Lauren K Williams Douglas R Mackay Madeline A Whitney Genevieve C Couldwell Wesley I Sundquist Katharine S Ullman |
author_sort |
Lauren K Williams |
title |
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing |
title_short |
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing |
title_full |
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing |
title_fullStr |
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing |
title_full_unstemmed |
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing |
title_sort |
identification of abscission checkpoint bodies as structures that regulate escrt factors to control abscission timing |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-08-01 |
description |
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, 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. |
topic |
abscission cell division ESCRT pathway cytokinesis |
url |
https://elifesciences.org/articles/63743 |
work_keys_str_mv |
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1717380563200901120 |