2. Academic Validation
  3. Mitosis. Microtubule detyrosination guides chromosomes during mitosis

Mitosis. Microtubule detyrosination guides chromosomes during mitosis

  • Science. 2015 May 15;348(6236):799-803. doi: 10.1126/science.aaa5175.
Marin Barisic 1,  Ricardo Silva e Sousa 2,  Suvranta K Tripathy 2,  Maria M Magiera 3,  Anatoly V Zaytsev 4,  Ana L Pereira 1,  Carsten Janke 3,  Ekaterina L Grishchuk 5,  Helder Maiato 6
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 3 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.
  • 4 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.
  • 5 Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [email protected] [email protected].
  • 6 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. [email protected] [email protected].
PMID: 25908662 DOI: 10.1126/science.aaa5175
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.

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