Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments
Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)–microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generate...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Rockefeller University Press
2013
|
| Online Access: | http://hdl.handle.net/1721.1/77175 https://orcid.org/0000-0002-3829-5612 |
| _version_ | 1811085122981593088 |
|---|---|
| author | Maia, Ana R. R. Garcia, Zaira Kabeche, Lilian Barisic, Marin Maffini, Stefano Macedo-Ribeiro, Sandra Compton, Duane A. Kaverina, Irina Maiato, Helder Cheeseman, Iain M |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Maia, Ana R. R. Garcia, Zaira Kabeche, Lilian Barisic, Marin Maffini, Stefano Macedo-Ribeiro, Sandra Compton, Duane A. Kaverina, Irina Maiato, Helder Cheeseman, Iain M |
| author_sort | Maia, Ana R. R. |
| collection | MIT |
| description | Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)–microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT–MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to KTs was enhanced by CLASP2 phosphorylation on S1234. This was specifically required to stabilize KT–MT attachments important for chromosome alignment and to coordinate KT and non-KT MT dynamics necessary to maintain spindle bipolarity. CLASP2 C-terminal phosphorylation by Plk1 was also required for chromosome alignment and timely satisfaction of the SAC. We propose that Cdk1 and Plk1 mediate a fine CLASP2 “phospho-switch” that temporally regulates KT–MT attachment stability. |
| first_indexed | 2024-09-23T13:03:15Z |
| format | Article |
| id | mit-1721.1/77175 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:03:15Z |
| publishDate | 2013 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/771752022-09-28T11:44:28Z Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments Maia, Ana R. R. Garcia, Zaira Kabeche, Lilian Barisic, Marin Maffini, Stefano Macedo-Ribeiro, Sandra Compton, Duane A. Kaverina, Irina Maiato, Helder Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Cheeseman, Iain McPherson Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)–microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT–MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to KTs was enhanced by CLASP2 phosphorylation on S1234. This was specifically required to stabilize KT–MT attachments important for chromosome alignment and to coordinate KT and non-KT MT dynamics necessary to maintain spindle bipolarity. CLASP2 C-terminal phosphorylation by Plk1 was also required for chromosome alignment and timely satisfaction of the SAC. We propose that Cdk1 and Plk1 mediate a fine CLASP2 “phospho-switch” that temporally regulates KT–MT attachment stability. National Institutes of Health (U.S.) (NIH/National Institute of General Medical Sciences grant GM088313) National Institutes of Health (U.S.) (NIH grant 5R01-GM078373) American Heart Association (grant-in-aid 10GRNT4230026) National Institutes of Health (U.S.) (NIH grant GM51542) Fundação para a Ciência e a Tecnologia (FCT grant REEQ/564/BIO/2005 (EU-FEDER), POCI 2010) 2013-02-21T16:25:36Z 2013-02-21T16:25:36Z 2012-03 2012-10 Article http://purl.org/eprint/type/JournalArticle 1540-8140 0021-9525 http://hdl.handle.net/1721.1/77175 Maia, A. R. R. et al. “Cdk1 and Plk1 Mediate a CLASP2 Phospho-switch That Stabilizes Kinetochore-microtubule Attachments.” The Journal of Cell Biology 199.2 (2012): 285–301. CrossRef. Web. https://orcid.org/0000-0002-3829-5612 en_US http://dx.doi.org/10.1083/jcb.201203091 Journal of Cell Biology Creative Commons Attribution 3.0 http://creativecommons.org/licenses/by/3.0/ application/pdf Rockefeller University Press Rockefeller UP |
| spellingShingle | Maia, Ana R. R. Garcia, Zaira Kabeche, Lilian Barisic, Marin Maffini, Stefano Macedo-Ribeiro, Sandra Compton, Duane A. Kaverina, Irina Maiato, Helder Cheeseman, Iain M Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title_full | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title_fullStr | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title_full_unstemmed | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title_short | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments |
| title_sort | cdk1 and plk1 mediate a clasp2 phospho switch that stabilizes kinetochore microtubule attachments |
| url | http://hdl.handle.net/1721.1/77175 https://orcid.org/0000-0002-3829-5612 |
| work_keys_str_mv | AT maiaanarr cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT garciazaira cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT kabechelilian cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT barisicmarin cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT maffinistefano cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT macedoribeirosandra cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT comptonduanea cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT kaverinairina cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT maiatohelder cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments AT cheesemaniainm cdk1andplk1mediateaclasp2phosphoswitchthatstabilizeskinetochoremicrotubuleattachments |