LTE1 promotes exit from mitosis by multiple mechanisms
In budding yeast, alignment of the anaphase spindle along the mother–bud axis is crucial for maintaining genome integrity. If the anaphase spindle becomes misaligned in the mother cell compartment, cells arrest in anaphase because the mitotic exit network (MEN), an essential Ras-like GTPase signalin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Society for Cell Biology
2017
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| Online Access: | http://hdl.handle.net/1721.1/107647 https://orcid.org/0000-0003-2910-9803 https://orcid.org/0000-0003-3019-2560 https://orcid.org/0000-0001-9837-0314 |
| _version_ | 1826193182049697792 |
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| author | Joyce, K. Whalen, J. Seshan, A. Falk, Jill E. Campbell, Ian Winsten Amon, Angelika B. |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Joyce, K. Whalen, J. Seshan, A. Falk, Jill E. Campbell, Ian Winsten Amon, Angelika B. |
| author_sort | Joyce, K. |
| collection | MIT |
| description | In budding yeast, alignment of the anaphase spindle along the mother–bud axis is crucial for maintaining genome integrity. If the anaphase spindle becomes misaligned in the mother cell compartment, cells arrest in anaphase because the mitotic exit network (MEN), an essential Ras-like GTPase signaling cascade, is inhibited by the spindle position checkpoint (SPoC). Distinct localization patterns of MEN and SPoC components mediate MEN inhibition. Most components of the MEN localize to spindle pole bodies. If the spindle becomes mispositioned in the mother cell compartment, cells arrest in anaphase due to inhibition of the MEN by the mother cell–restricted SPoC kinase Kin4. Here we show that a bud-localized activating signal is necessary for full MEN activation. We identify Lte1 as this signal and show that Lte1 activates the MEN in at least two ways. It inhibits small amounts of Kin4 that are present in the bud via its central domain. An additional MEN-activating function of Lte1 is mediated by its N- and C-terminal GEF domains, which, we propose, directly activate the MEN GTPase Tem1. We conclude that control of the MEN by spindle position is exerted by both negative and positive regulatory elements that control the pathway’s GTPase activity. |
| first_indexed | 2024-09-23T09:35:00Z |
| format | Article |
| id | mit-1721.1/107647 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:35:00Z |
| publishDate | 2017 |
| publisher | American Society for Cell Biology |
| record_format | dspace |
| spelling | mit-1721.1/1076472022-09-26T12:28:27Z LTE1 promotes exit from mitosis by multiple mechanisms Joyce, K. Whalen, J. Seshan, A. Falk, Jill E. Campbell, Ian Winsten Amon, Angelika B. Koch Institute for Integrative Cancer Research at MIT Falk, Jill E. Campbell, Ian Winsten Amon, Angelika B. In budding yeast, alignment of the anaphase spindle along the mother–bud axis is crucial for maintaining genome integrity. If the anaphase spindle becomes misaligned in the mother cell compartment, cells arrest in anaphase because the mitotic exit network (MEN), an essential Ras-like GTPase signaling cascade, is inhibited by the spindle position checkpoint (SPoC). Distinct localization patterns of MEN and SPoC components mediate MEN inhibition. Most components of the MEN localize to spindle pole bodies. If the spindle becomes mispositioned in the mother cell compartment, cells arrest in anaphase due to inhibition of the MEN by the mother cell–restricted SPoC kinase Kin4. Here we show that a bud-localized activating signal is necessary for full MEN activation. We identify Lte1 as this signal and show that Lte1 activates the MEN in at least two ways. It inhibits small amounts of Kin4 that are present in the bud via its central domain. An additional MEN-activating function of Lte1 is mediated by its N- and C-terminal GEF domains, which, we propose, directly activate the MEN GTPase Tem1. We conclude that control of the MEN by spindle position is exerted by both negative and positive regulatory elements that control the pathway’s GTPase activity. National Institutes of Health (U.S.) (Grant HD085866) National Cancer Institute (U.S.) David H. Koch Institute for Integrative Cancer Research at MIT. Support (Core) (Grant P30-CA14051) 2017-03-22T17:49:14Z 2017-03-22T17:49:14Z 2016-10 2016-09 Article http://purl.org/eprint/type/JournalArticle 1059-1524 http://hdl.handle.net/1721.1/107647 Falk, J. E. et al. “LTE1 Promotes Exit from Mitosis by Multiple Mechanisms.” Molecular Biology of the Cell 27.25 (2016): 3991–4001. https://orcid.org/0000-0003-2910-9803 https://orcid.org/0000-0003-3019-2560 https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1091/mbc.E16-08-0563 Molecular Biology of the Cell Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Society for Cell Biology American Society for Cell Biology |
| spellingShingle | Joyce, K. Whalen, J. Seshan, A. Falk, Jill E. Campbell, Ian Winsten Amon, Angelika B. LTE1 promotes exit from mitosis by multiple mechanisms |
| title | LTE1 promotes exit from mitosis by multiple mechanisms |
| title_full | LTE1 promotes exit from mitosis by multiple mechanisms |
| title_fullStr | LTE1 promotes exit from mitosis by multiple mechanisms |
| title_full_unstemmed | LTE1 promotes exit from mitosis by multiple mechanisms |
| title_short | LTE1 promotes exit from mitosis by multiple mechanisms |
| title_sort | lte1 promotes exit from mitosis by multiple mechanisms |
| url | http://hdl.handle.net/1721.1/107647 https://orcid.org/0000-0003-2910-9803 https://orcid.org/0000-0003-3019-2560 https://orcid.org/0000-0001-9837-0314 |
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