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CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation
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Davies, Tim, Kodera, Noriyuki, Kaminski Schierle, Gabriele S., Rees, Eric, Erdelyi, Miklos, Kaminski, Clemens F., Ando, Toshio and Mishima, Masanori (2015) CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation. PLoS Biology, Volume 13 (Number 4). Article number e1002121. doi:10.1371/journal.pbio.1002121
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Official URL: http://dx.doi.org/10.1371/journal.pbio.1002121
Abstract
Centralspindlin, a constitutive 2:2 heterotetramer of MKLP1 (a kinesin-6) and the non-motor subunit CYK4, plays important roles in cytokinesis. It is crucial for the formation of central spindle microtubule bundle structure. Its accumulation at the central antiparallel overlap zone is key for recruitment and regulation of downstream cytokinesis factors and for stable anchoring of the plasma membrane at the midbody. Both MKLP1 and CYK4 are required for efficient microtubule bundling. However, the mechanism by which CYK4 contributes to this is unclear. Here we performed structural and functional analyses of centralspindlin using high-speed atomic force microscopy, Fӧrster resonance energy transfer analysis, and in vitro reconstitution. Our data reveal that CYK4 binds to a globular mass in the atypically long MKLP1 neck domain between the catalytic core and the coiled coil and thereby reconfigures the two motor domains in the MKLP1 dimer to be suitable for antiparallel microtubule bundling. Our work provides insights into the microtubule bundling during cytokinesis and into the working mechanisms of the kinesins with non-canonical neck structures.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history | ||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cytokinesis | ||||||||
| Journal or Publication Title: | PLoS Biology | ||||||||
| Publisher: | Public Library of Science | ||||||||
| ISSN: | 1545-7885 | ||||||||
| Official Date: | 13 April 2015 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 29 December 2015 | ||||||||
| Volume: | Volume 13 | ||||||||
| Number: | Number 4 | ||||||||
| Article Number: | Article number e1002121 | ||||||||
| DOI: | 10.1371/journal.pbio.1002121 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Cancer Research UK (CRUK), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Heiwa Nakajima Foundation, Japan. Monbushō, Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC), Alzheimer's Research UK, Engineering and Physical Sciences Research Council (EPSRC) | ||||||||
| Grant number: | C19769/A6356 (CRUK), C19769/A11985 (CRUK), C19769/A7164 (CRUK), 20221006 (MEXT), 089703/Z/09/Z (MRC), MR/K015850/1 (MRC), ARUK-EG2012A-1 (ARUK), EP/H018301/1 (EPSRC) |
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