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Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation

In the early Caenorhabditis elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows...

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Autores principales: Longhini, Katrina M, Glotzer, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799973/
https://www.ncbi.nlm.nih.gov/pubmed/36533896
http://dx.doi.org/10.7554/eLife.83992
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author Longhini, Katrina M
Glotzer, Michael
author_facet Longhini, Katrina M
Glotzer, Michael
author_sort Longhini, Katrina M
collection PubMed
description In the early Caenorhabditis elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows, due to an inhibitory activity that depends on aster positioning relative to the polar cortices. Here, we show polar relaxation is associated with depletion of cortical ECT-2, a RhoGEF, specifically at the posterior cortex. Asymmetric ECT-2 accumulation requires intact centrosomes, Aurora A (AIR-1), and myosin-dependent cortical flows. Within a localization competent ECT-2 fragment, we identified three putative phospho-acceptor sites in the PH domain of ECT-2 that render ECT-2 responsive to inhibition by AIR-1. During both polarization and cytokinesis, our results suggest that centrosomal AIR-1 breaks symmetry via ECT-2 phosphorylation; this local inhibition of ECT-2 is amplified by myosin-driven flows that generate regional ECT-2 asymmetry. Together, these mechanisms cooperate to induce polarized assembly of cortical myosin, contributing to both embryo polarization and cytokinesis.
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spelling pubmed-97999732022-12-30 Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation Longhini, Katrina M Glotzer, Michael eLife Cell Biology In the early Caenorhabditis elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows, due to an inhibitory activity that depends on aster positioning relative to the polar cortices. Here, we show polar relaxation is associated with depletion of cortical ECT-2, a RhoGEF, specifically at the posterior cortex. Asymmetric ECT-2 accumulation requires intact centrosomes, Aurora A (AIR-1), and myosin-dependent cortical flows. Within a localization competent ECT-2 fragment, we identified three putative phospho-acceptor sites in the PH domain of ECT-2 that render ECT-2 responsive to inhibition by AIR-1. During both polarization and cytokinesis, our results suggest that centrosomal AIR-1 breaks symmetry via ECT-2 phosphorylation; this local inhibition of ECT-2 is amplified by myosin-driven flows that generate regional ECT-2 asymmetry. Together, these mechanisms cooperate to induce polarized assembly of cortical myosin, contributing to both embryo polarization and cytokinesis. eLife Sciences Publications, Ltd 2022-12-19 /pmc/articles/PMC9799973/ /pubmed/36533896 http://dx.doi.org/10.7554/eLife.83992 Text en © 2022, Longhini and Glotzer https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Longhini, Katrina M
Glotzer, Michael
Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title_full Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title_fullStr Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title_full_unstemmed Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title_short Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
title_sort aurora a and cortical flows promote polarization and cytokinesis by inducing asymmetric ect-2 accumulation
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799973/
https://www.ncbi.nlm.nih.gov/pubmed/36533896
http://dx.doi.org/10.7554/eLife.83992
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