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Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
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Castrogiovanni, Cédric, Inchingolo, Alessio, Harrison, Jonathan U., Dudka, Damian, Sen, Onur, Burroughs, Nigel John, McAinsh, Andrew D. and Meraldi, Patrick (2022) Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules. Nature Communications, 13 . 4704. doi:10.1038/s41467-022-32421-x ISSN 2041-1723.
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WRAP-Evidence-HURP-EB-free-nucleotide-zone-kinetochore-microtubules-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (12Mb) | Preview |
Official URL: https://doi.org/10.1038/s41467-022-32421-x
Abstract
Current models infer that the microtubule-based mitotic spindle is built from GDP-tubulin with small GTP caps at microtubule plus-ends, including those that attach to kinetochores, forming the kinetochore-fibres. Here we reveal that kinetochore-fibres additionally contain a dynamic mixed-nucleotide zone that reaches several microns in length. This zone becomes visible in cells expressing fluorescently labelled end-binding proteins, a known marker for GTP-tubulin, and endogenously-labelled HURP - a protein which we show to preferentially bind the GDP microtubule lattice in vitro and in vivo. We find that in mitotic cells HURP accumulates on the kinetochore-proximal region of depolymerising kinetochore-fibres, whilst avoiding recruitment to nascent polymerising K-fibres, giving rise to a growing “HURP-gap”. The absence of end-binding proteins in the HURP-gaps leads us to postulate that they reflect a mixed-nucleotide zone. We generate a minimal quantitative model based on the preferential binding of HURP to GDP-tubulin to show that such a mixed-nucleotide zone is sufficient to recapitulate the observed in vivo dynamics of HURP-gaps.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology | |||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Spindle (Cell division), Microtubules, Chromosomes, Guanosine triphosphate | |||||||||||||||
| Journal or Publication Title: | Nature Communications | |||||||||||||||
| Publisher: | Nature Publishing Group UK | |||||||||||||||
| ISSN: | 2041-1723 | |||||||||||||||
| Official Date: | 10 August 2022 | |||||||||||||||
| Dates: |
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| Volume: | 13 | |||||||||||||||
| Article Number: | 4704 | |||||||||||||||
| DOI: | 10.1038/s41467-022-32421-x | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Reuse Statement (publisher, data, author rights): | ** From Springer Nature via Jisc Publications Router ** History: received 11-08-2021; accepted 28-07-2022; registration 01-08-2022; pub-electronic 10-08-2022; online 10-08-2022; collection 12-2022. ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Date of first compliant deposit: | 1 September 2022 | |||||||||||||||
| Date of first compliant Open Access: | 1 September 2022 | |||||||||||||||
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