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CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments
CLASPs are conserved microtubule plus-end–tracking proteins that suppress microtubule catastrophes and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore–microtubule dynamics required for chromosome segregation fidelity, but the underly...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041679/ https://www.ncbi.nlm.nih.gov/pubmed/31757788 http://dx.doi.org/10.1083/jcb.201905080 |
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author | Girão, Hugo Okada, Naoyuki Rodrigues, Tony A. Silva, Alexandra O. Figueiredo, Ana C. Garcia, Zaira Moutinho-Santos, Tatiana Hayashi, Ikuko Azevedo, Jorge E. Macedo-Ribeiro, Sandra Maiato, Helder |
author_facet | Girão, Hugo Okada, Naoyuki Rodrigues, Tony A. Silva, Alexandra O. Figueiredo, Ana C. Garcia, Zaira Moutinho-Santos, Tatiana Hayashi, Ikuko Azevedo, Jorge E. Macedo-Ribeiro, Sandra Maiato, Helder |
author_sort | Girão, Hugo |
collection | PubMed |
description | CLASPs are conserved microtubule plus-end–tracking proteins that suppress microtubule catastrophes and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore–microtubule dynamics required for chromosome segregation fidelity, but the underlying mechanism remains unknown. Here, we found that human CLASP2 exists predominantly as a monomer in solution, but it can self-associate through its C-terminal kinetochore-binding domain. Kinetochore localization was independent of self-association, and driving monomeric CLASP2 to kinetochores fully rescued normal kinetochore–microtubule dynamics, while partially sustaining mitosis. CLASP2 kinetochore localization, recognition of growing microtubule plus-ends through EB–protein interaction, and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains independently sustained normal spindle length, timely spindle assembly checkpoint satisfaction, chromosome congression, and faithful segregation. Measurements of kinetochore–microtubule half-life and poleward flux revealed that CLASP2 regulates kinetochore–microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore–microtubule interface. We propose that kinetochore CLASP2 suppresses microtubule depolymerization and detachment by binding to curved protofilaments at microtubule plus-ends. |
format | Online Article Text |
id | pubmed-7041679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70416792020-03-03 CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments Girão, Hugo Okada, Naoyuki Rodrigues, Tony A. Silva, Alexandra O. Figueiredo, Ana C. Garcia, Zaira Moutinho-Santos, Tatiana Hayashi, Ikuko Azevedo, Jorge E. Macedo-Ribeiro, Sandra Maiato, Helder J Cell Biol Research Articles CLASPs are conserved microtubule plus-end–tracking proteins that suppress microtubule catastrophes and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore–microtubule dynamics required for chromosome segregation fidelity, but the underlying mechanism remains unknown. Here, we found that human CLASP2 exists predominantly as a monomer in solution, but it can self-associate through its C-terminal kinetochore-binding domain. Kinetochore localization was independent of self-association, and driving monomeric CLASP2 to kinetochores fully rescued normal kinetochore–microtubule dynamics, while partially sustaining mitosis. CLASP2 kinetochore localization, recognition of growing microtubule plus-ends through EB–protein interaction, and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains independently sustained normal spindle length, timely spindle assembly checkpoint satisfaction, chromosome congression, and faithful segregation. Measurements of kinetochore–microtubule half-life and poleward flux revealed that CLASP2 regulates kinetochore–microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore–microtubule interface. We propose that kinetochore CLASP2 suppresses microtubule depolymerization and detachment by binding to curved protofilaments at microtubule plus-ends. Rockefeller University Press 2019-11-22 /pmc/articles/PMC7041679/ /pubmed/31757788 http://dx.doi.org/10.1083/jcb.201905080 Text en © 2019 Girão et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Girão, Hugo Okada, Naoyuki Rodrigues, Tony A. Silva, Alexandra O. Figueiredo, Ana C. Garcia, Zaira Moutinho-Santos, Tatiana Hayashi, Ikuko Azevedo, Jorge E. Macedo-Ribeiro, Sandra Maiato, Helder CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title | CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title_full | CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title_fullStr | CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title_full_unstemmed | CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title_short | CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
title_sort | clasp2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041679/ https://www.ncbi.nlm.nih.gov/pubmed/31757788 http://dx.doi.org/10.1083/jcb.201905080 |
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