Eph-mediated tyrosine phosphorylation of citron kinase controls abscission

• Published in: The Journal of cell biology Vol. 214; no. 5; pp. 555 - 569
• Main Authors: Jungas, Thomas, Perchey, Renaud T, Fawal, Mohamad, Callot, Caroline, Froment, Carine, Burlet-Schiltz, Odile, Besson, Arnaud, Davy, Alice
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 29.08.2016; The Rockefeller University Press
• Subjects: Amino Acid Sequence; Animals; Cell Death; Cell division; Cells; Cytokines; Cytokinesis; Ephrin-B2 - metabolism; Female; HEK293 Cells; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - metabolism; Life Sciences; Male; Mice; Phosphorylation; Phosphotyrosine - metabolism; Protein Binding; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction; src-Family Kinases - metabolism; Telophase; Tyrosine - metabolism; ETD, electron transfer dissociation; E, embryonic day; CID, collision-induced dissociation CitK, citron kinase coIP, coimmunoprecipitation E, embryonic day ETD, electron transfer dissociation FL, full-length ICB, intercellular bridge IF, immunofluorescence IP, immunoprecipitation; CID, collision-induced dissociation; CitK, citron kinase; coIP, coimmunoprecipitation; IF, immunofluorescence; IP, immunoprecipitation; FL, full-length; ICB, intercellular bridge
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201602057

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.