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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Main Authors: Katrina M Longhini, Michael Glotzer
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/83992
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author Katrina M Longhini
Michael Glotzer
author_facet Katrina M Longhini
Michael Glotzer
author_sort Katrina M Longhini
collection DOAJ
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 doaj.art-a10debc78ed84f8ba4c0608c8c616a102022-12-29T15:59:23ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83992Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulationKatrina M Longhini0https://orcid.org/0000-0002-6600-7083Michael Glotzer1https://orcid.org/0000-0002-8723-7232Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United StatesDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United StatesIn 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.https://elifesciences.org/articles/83992cytokinesispolarizationCaenorhabditis elegansRho GTPaseRhoGEFAurora A
spellingShingle Katrina M Longhini
Michael Glotzer
Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
eLife
cytokinesis
polarization
Caenorhabditis elegans
Rho GTPase
RhoGEF
Aurora A
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 cytokinesis
polarization
Caenorhabditis elegans
Rho GTPase
RhoGEF
Aurora A
url https://elifesciences.org/articles/83992
work_keys_str_mv AT katrinamlonghini auroraaandcorticalflowspromotepolarizationandcytokinesisbyinducingasymmetricect2accumulation
AT michaelglotzer auroraaandcorticalflowspromotepolarizationandcytokinesisbyinducingasymmetricect2accumulation