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Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation
Open accessPreprint — published as 10.7554/elife.83992
Abstract
In the early C. 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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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Longhini, K. M., & Glotzer, M.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Glotzer, Michael
- Venue
- eLife
- Publisher
- openRxiv
- Published
- 2022-05-25
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9799973
- OpenAlex
- W4313405134
- Cited by
- 14
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- University of Chicago (cc-by)
- Funders
- École Polytechnique Fédérale de Lausanne
- National Institutes of Health (OD010440, P40OD010440)
- National Institute of General Medical Sciences (R35GM127091)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- AURKA, RhoGEF, cell polarization, cytokinesis, centrosome, pleckstrin homology domain, centralspindlin, Caenorhabditis elegans embryo, posterior cortex
- MeSH terms
- Animals, Myosins, Caenorhabditis elegans, Guanine Nucleotide Exchange Factors, Caenorhabditis elegans Proteins, Cytokinesis, Rho Guanine Nucleotide Exchange Factors, Aurora Kinase A
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