title: Eph-mediated tyrosine phosphorylation of citron kinase controls abscission.
abstract: 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.
authors.affiliation: Centre de Biologie du Développement, Centre de Biologie Intégrative, Université de Toulouse, Centre National de la Recherche Scientifique, Université Paul Sabatier, 31062 Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jungas
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1037, Cancer Research Center of Toulouse, 31037 Toulouse, France Centre National de la Recherche Scientifique, ERL 5294, Université de Toulouse, Université Paul Sabatier, 31037 Toulouse, France.
authors.forename: Renaud T
authors.initials: RT
authors.lastname: Perchey
authors.affiliation: Centre de Biologie du Développement, Centre de Biologie Intégrative, Université de Toulouse, Centre National de la Recherche Scientifique, Université Paul Sabatier, 31062 Toulouse, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Fawal
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1037, Cancer Research Center of Toulouse, 31037 Toulouse, France Centre National de la Recherche Scientifique, ERL 5294, Université de Toulouse, Université Paul Sabatier, 31037 Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Callot
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Froment
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1037, Cancer Research Center of Toulouse, 31037 Toulouse, France Centre National de la Recherche Scientifique, ERL 5294, Université de Toulouse, Université Paul Sabatier, 31037 Toulouse, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Besson
authors.affiliation: Centre de Biologie du Développement, Centre de Biologie Intégrative, Université de Toulouse, Centre National de la Recherche Scientifique, Université Paul Sabatier, 31062 Toulouse, France alice.davy@univ-tlse3.fr.
authors.forename: Alice
authors.initials: A
authors.lastname: Davy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D048749:Cytokinesis; D036388:Ephrin-B2 / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013692:Telophase; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D036388:Ephrin-B2; D047908:Intracellular Signaling Peptides and Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; C115635:citron-kinase; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases