title: Mitosis. Microtubule detyrosination guides chromosomes during mitosis.
abstract: Before chromosomes segregate into daughter cells, they align at the mitotic spindle equator, a process known as chromosome congression. Centromere-associated protein E (CENP-E)/Kinesin-7 is a microtubule plus-end-directed kinetochore motor required for congression of pole-proximal chromosomes. Because the plus-ends of many astral microtubules in the spindle point to the cell cortex, it remains unknown how CENP-E guides pole-proximal chromosomes specifically toward the equator. We found that congression of pole-proximal chromosomes depended on specific posttranslational detyrosination of spindle microtubules that point to the equator. In vitro reconstitution experiments demonstrated that CENP-E-dependent transport was strongly enhanced on detyrosinated microtubules. Blocking tubulin tyrosination in cells caused ubiquitous detyrosination of spindle microtubules, and CENP-E transported chromosomes away from spindle poles in random directions. Thus, CENP-E-driven chromosome congression is guided by microtubule detyrosination.
authors.affiliation: Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Portugal.
authors.forename: Marin
authors.initials: M
authors.lastname: Barisic
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silva e Sousa
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Suvranta K
authors.initials: SK
authors.lastname: Tripathy
authors.affiliation: Institut Curie, 91405 Orsay, France. Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France. Centre National de la Recherche Scientifique UMR 3348, 91405 Orsay, France.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Magiera
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences (RAS), Moscow, Russia. Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Zaytsev
authors.affiliation: Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Portugal.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Pereira
authors.affiliation: Institut Curie, 91405 Orsay, France. Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France. Centre National de la Recherche Scientifique UMR 3348, 91405 Orsay, France.
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. maiato@ibmc.up.pt gekate@mail.med.upenn.edu.
authors.forename: Ekaterina L
authors.initials: EL
authors.lastname: Grishchuk
authors.affiliation: Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Instituto de Investigação e Inovação em Saúde-i3S, Universidade do Porto, Portugal. Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal. maiato@ibmc.up.pt gekate@mail.med.upenn.edu.
authors.forename: Helder
authors.initials: H
authors.lastname: Maiato
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D057054:Molecular Imaging; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002868:Chromosomal Proteins, Non-Histone; C571460:GSK923295; D014404:Tubulin; C068688:centromere protein E; D014443:Tyrosine; D012521:Sarcosine