Cargando…

“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...

Descripción completa

Detalles Bibliográficos
Autores principales: Heasley, Lydia R., Markus, Steven M., DeLuca, Jennifer G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
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
_version_ 1783233450068672512
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
work_keys_str_mv AT heasleylydiar waitanaphasesignalsarenotconfinedtothemitoticspindle
AT markusstevenm waitanaphasesignalsarenotconfinedtothemitoticspindle
AT delucajenniferg waitanaphasesignalsarenotconfinedtothemitoticspindle