Publication Date:
2015-04-25
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506776/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barisic, Marin -- Silva e Sousa, Ricardo -- Tripathy, Suvranta K -- Magiera, Maria M -- Zaytsev, Anatoly V -- Pereira, Ana L -- Janke, Carsten -- Grishchuk, Ekaterina L -- Maiato, Helder -- R01 GM098389/GM/NIGMS NIH HHS/ -- R01-GM098389/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):799-803. doi: 10.1126/science.aaa5175. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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 Investigacao e Inovacao em Saude-i3S, Universidade do Porto, Portugal. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. ; 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. ; 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. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. maiato@ibmc.up.pt gekate@mail.med.upenn.edu. ; 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 Investigacao e Inovacao em Saude-i3S, Universidade do Porto, Portugal. Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal. maiato@ibmc.up.pt gekate@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908662" target="_blank"〉PubMed〈/a〉
Keywords:
Bicyclo Compounds, Heterocyclic/pharmacology
;
Cell Line, Tumor
;
Chromosomal Proteins, Non-Histone/antagonists & inhibitors/genetics/*metabolism
;
*Chromosome Segregation
;
Humans
;
Microtubules/*metabolism
;
*Mitosis
;
Molecular Imaging
;
Sarcosine/analogs & derivatives/pharmacology
;
Spindle Apparatus/metabolism
;
Tubulin/metabolism
;
Tyrosine/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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