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“Wait anaphase” signals are not confined to the mitotic spindle
The spindle assembly checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. This is achieved through inhibition of the anaphase-promoting complex/cyclosome by a kinetochore-derived “wa...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415015/ https://www.ncbi.nlm.nih.gov/pubmed/28298492 http://dx.doi.org/10.1091/mbc.E17-01-0036 |
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author | Heasley, Lydia R. Markus, Steven M. DeLuca, Jennifer G. |
author_facet | Heasley, Lydia R. Markus, Steven M. DeLuca, Jennifer G. |
author_sort | Heasley, Lydia R. |
collection | PubMed |
description | The spindle assembly checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. This is achieved through inhibition of the anaphase-promoting complex/cyclosome by a kinetochore-derived “wait anaphase” signal known as the mitotic checkpoint complex. It remains unclear whether the localization and activity of these inhibitory complexes are restricted to the mitotic spindle compartment or are diffusible throughout the cytoplasm. Here we report that “wait anaphase” signals are indeed able to diffuse outside the confines of the mitotic spindle compartment. Using a cell fusion approach to generate multinucleate cells, we investigate the effects of checkpoint signals derived from one spindle compartment on a neighboring spindle compartment. We find that spindle compartments in close proximity wait for one another to align all chromosomes before entering anaphase synchronously. Synchrony is disrupted in cells with increased interspindle distances and cellular constrictions between spindle compartments. In addition, when mitotic cells are fused with interphase cells, “wait anaphase” signals are diluted, resulting in premature mitotic exit. Overall our studies reveal that anaphase inhibitors are diffusible and active outside the confines of the mitotic spindle from which they are derived. |
format | Online Article Text |
id | pubmed-5415015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-54150152017-07-16 “Wait anaphase” signals are not confined to the mitotic spindle Heasley, Lydia R. Markus, Steven M. DeLuca, Jennifer G. Mol Biol Cell Articles The spindle assembly checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. This is achieved through inhibition of the anaphase-promoting complex/cyclosome by a kinetochore-derived “wait anaphase” signal known as the mitotic checkpoint complex. It remains unclear whether the localization and activity of these inhibitory complexes are restricted to the mitotic spindle compartment or are diffusible throughout the cytoplasm. Here we report that “wait anaphase” signals are indeed able to diffuse outside the confines of the mitotic spindle compartment. Using a cell fusion approach to generate multinucleate cells, we investigate the effects of checkpoint signals derived from one spindle compartment on a neighboring spindle compartment. We find that spindle compartments in close proximity wait for one another to align all chromosomes before entering anaphase synchronously. Synchrony is disrupted in cells with increased interspindle distances and cellular constrictions between spindle compartments. In addition, when mitotic cells are fused with interphase cells, “wait anaphase” signals are diluted, resulting in premature mitotic exit. Overall our studies reveal that anaphase inhibitors are diffusible and active outside the confines of the mitotic spindle from which they are derived. The American Society for Cell Biology 2017-05-01 /pmc/articles/PMC5415015/ /pubmed/28298492 http://dx.doi.org/10.1091/mbc.E17-01-0036 Text en © 2017 Heasley et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Heasley, Lydia R. Markus, Steven M. DeLuca, Jennifer G. “Wait anaphase” signals are not confined to the mitotic spindle |
title | “Wait anaphase” signals are not confined to the mitotic spindle |
title_full | “Wait anaphase” signals are not confined to the mitotic spindle |
title_fullStr | “Wait anaphase” signals are not confined to the mitotic spindle |
title_full_unstemmed | “Wait anaphase” signals are not confined to the mitotic spindle |
title_short | “Wait anaphase” signals are not confined to the mitotic spindle |
title_sort | “wait anaphase” signals are not confined to the mitotic spindle |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415015/ https://www.ncbi.nlm.nih.gov/pubmed/28298492 http://dx.doi.org/10.1091/mbc.E17-01-0036 |
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