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Eph-mediated tyrosine phosphorylation of citron kinase controls abscission

Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-k...

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Autores principales: Jungas, Thomas, Perchey, Renaud T., Fawal, Mohamad, Callot, Caroline, Froment, Carine, Burlet-Schiltz, Odile, Besson, Arnaud, Davy, Alice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004443/
https://www.ncbi.nlm.nih.gov/pubmed/27551053
http://dx.doi.org/10.1083/jcb.201602057
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author Jungas, Thomas
Perchey, Renaud T.
Fawal, Mohamad
Callot, Caroline
Froment, Carine
Burlet-Schiltz, Odile
Besson, Arnaud
Davy, Alice
author_facet Jungas, Thomas
Perchey, Renaud T.
Fawal, Mohamad
Callot, Caroline
Froment, Carine
Burlet-Schiltz, Odile
Besson, Arnaud
Davy, Alice
author_sort Jungas, Thomas
collection PubMed
description Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis.
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spelling pubmed-50044432017-02-28 Eph-mediated tyrosine phosphorylation of citron kinase controls abscission Jungas, Thomas Perchey, Renaud T. Fawal, Mohamad Callot, Caroline Froment, Carine Burlet-Schiltz, Odile Besson, Arnaud Davy, Alice J Cell Biol Research Articles Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis. The Rockefeller University Press 2016-08-29 /pmc/articles/PMC5004443/ /pubmed/27551053 http://dx.doi.org/10.1083/jcb.201602057 Text en © 2016 Jungas et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Jungas, Thomas
Perchey, Renaud T.
Fawal, Mohamad
Callot, Caroline
Froment, Carine
Burlet-Schiltz, Odile
Besson, Arnaud
Davy, Alice
Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title_full Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title_fullStr Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title_full_unstemmed Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title_short Eph-mediated tyrosine phosphorylation of citron kinase controls abscission
title_sort eph-mediated tyrosine phosphorylation of citron kinase controls abscission
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004443/
https://www.ncbi.nlm.nih.gov/pubmed/27551053
http://dx.doi.org/10.1083/jcb.201602057
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