Clathrin's adaptor interaction sites are repurposed to stabilize microtubules during mitosis
| Autor: | Shweta Bendre, Tanja Bange, Alexander W. Bird, Per O. Widlund, Lisa Mazul, Divya Singh, Arnaud Rondelet, Ingrid R. Vetter, Harish C. Thakur, Andreas Hecker, Franziska Müller, Arthur T. Porfetye, Pia Brinkert, Michael Hiller, Nadine Schmidt, Yu-Chih Lin |
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| Rok vydání: | 2019 |
| Předmět: |
Endocytic cycle
Kinesins Mitosis Cell Cycle Proteins Spindle Apparatus Clathrin Microtubules Biochemistry Article 03 medical and health sciences Mice 0302 clinical medicine Microtubule Chromosome Segregation Animals Humans Kinetochores Cytoskeleton 030304 developmental biology 0303 health sciences biology Kinetochore Vesicle Mouse Embryonic Stem Cells Cell Biology Cell biology Spindle apparatus Clathrin Heavy Chains biology.protein Astral microtubules Microtubule-Associated Proteins 030217 neurology & neurosurgery Cell Cycle and Division |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Clathrin stabilizes microtubules and promotes chromosome alignment during mitosis. Rondelet et al. show that the clathrin–adaptor interaction mechanism is repurposed to recruit GTSE1 to the spindle, which inhibits the microtubule depolymerase MCAK and promotes chromosome alignment by stabilizing nonkinetochore microtubules. Clathrin ensures mitotic spindle stability and efficient chromosome alignment, independently of its vesicle trafficking function. Although clathrin localizes to the mitotic spindle and kinetochore fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules are unclear. We show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the spindle. Structural analyses reveal that these sites interact directly with clathrin-box motifs on GTSE1. Disruption of this interaction releases GTSE1 from spindles, causing defects in chromosome alignment. Surprisingly, this disruption destabilizes astral microtubules, but not kinetochore-microtubule attachments, and chromosome alignment defects are due to a failure of chromosome congression independent of kinetochore–microtubule attachment stability. GTSE1 recruited to the spindle by clathrin stabilizes microtubules by inhibiting the microtubule depolymerase MCAK. This work uncovers a novel role of clathrin adaptor-type interactions to stabilize nonkinetochore fiber microtubules to support chromosome congression, defining for the first time a repurposing of this endocytic interaction mechanism during mitosis. |
| Databáze: | OpenAIRE |
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