Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin
Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homol ogs segregate at anaphase I. The Shugoshin proteins preserve cent...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
Proceedings of the National Academy of Sciences
2020
|
| Online Access: | https://hdl.handle.net/1721.1/124801 |
| _version_ | 1826213484179750912 |
|---|---|
| author | Pinto, Belinda S. Orr-Weaver, Terry L. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Pinto, Belinda S. Orr-Weaver, Terry L. |
| author_sort | Pinto, Belinda S. |
| collection | MIT |
| description | Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homol ogs segregate at anaphase I. The Shugoshin proteins preserve centromere cohesion by protecting the cohesin complex from cleavage, and this has been shown in yeasts to be mediated by recruitment of the protein phosphatase 2A B′ (PP2A B′). In metazoans, delineation of the role of PP2A B′ in meiosis has been hindered by its myriad of other essential roles. The Drosophila Shugoshin MEI-S332 can bind directly to both of the B′ regulatory subunits of PP2A, Wdb and Wrd, in yeast two-hybrid experiments. Exploiting experimental advantages of Drosophila spermatogenesis, we found that the Wdb subunit localizes first along chromosomes in meiosis I, becoming restricted to the centromere region as MEI-S332 binds. Wdb and MEI-S332 show colocalization at the centromere region until release of sister-chromatid cohesion at the metaphase II/anaphase II transition. MEI-S332 is necessary for Wdb localization, but, additionally, both Wdb and Wrd are required for MEI-S332 localization. Thus, rather than MEI-S332 being hierarchical to PP2A B′, these proteins reciprocally ensure centromere localization of the complex. We analyzed functional relationships between MEI-S332 and the two forms of PP2A by quantifying meiotic chromosome segregation defects in double or triple mutants. These studies revealed that both Wdb and Wrd contribute to MEI-S332’s ability to ensure accurate segregation of sister chromatids, but, as in centromere localization, they do not act solely downstream of MEI-S332. ©2017 |
| first_indexed | 2024-09-23T15:49:56Z |
| format | Article |
| id | mit-1721.1/124801 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:49:56Z |
| publishDate | 2020 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1248012022-09-29T16:28:23Z Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin Pinto, Belinda S. Orr-Weaver, Terry L. Whitehead Institute for Biomedical Research Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homol ogs segregate at anaphase I. The Shugoshin proteins preserve centromere cohesion by protecting the cohesin complex from cleavage, and this has been shown in yeasts to be mediated by recruitment of the protein phosphatase 2A B′ (PP2A B′). In metazoans, delineation of the role of PP2A B′ in meiosis has been hindered by its myriad of other essential roles. The Drosophila Shugoshin MEI-S332 can bind directly to both of the B′ regulatory subunits of PP2A, Wdb and Wrd, in yeast two-hybrid experiments. Exploiting experimental advantages of Drosophila spermatogenesis, we found that the Wdb subunit localizes first along chromosomes in meiosis I, becoming restricted to the centromere region as MEI-S332 binds. Wdb and MEI-S332 show colocalization at the centromere region until release of sister-chromatid cohesion at the metaphase II/anaphase II transition. MEI-S332 is necessary for Wdb localization, but, additionally, both Wdb and Wrd are required for MEI-S332 localization. Thus, rather than MEI-S332 being hierarchical to PP2A B′, these proteins reciprocally ensure centromere localization of the complex. We analyzed functional relationships between MEI-S332 and the two forms of PP2A by quantifying meiotic chromosome segregation defects in double or triple mutants. These studies revealed that both Wdb and Wrd contribute to MEI-S332’s ability to ensure accurate segregation of sister chromatids, but, as in centromere localization, they do not act solely downstream of MEI-S332. ©2017 NSF (grant no. MCB0646593) 2020-04-22T16:26:27Z 2020-04-22T16:26:27Z 2017-12 2017-10 2018-06-13T16:00:50Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/124801 Pinto, Belinda S., and Terry L. Orr-Weaver, "Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin." Proceedings of the National Academy of Sciences 114, 49 (December 2017): p. 12988-93 doi 10.1073/PNAS.1718450114 ©2017 Author(s) 10.1073/PNAS.1718450114 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Pinto, Belinda S. Orr-Weaver, Terry L. Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title | Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title_full | Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title_fullStr | Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title_full_unstemmed | Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title_short | Drosophila protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin |
| title_sort | drosophila protein phosphatases 2a b wdb and wrd regulate meiotic centromere localization and function of the mei s332 shugoshin |
| url | https://hdl.handle.net/1721.1/124801 |
| work_keys_str_mv | AT pintobelindas drosophilaproteinphosphatases2abwdbandwrdregulatemeioticcentromerelocalizationandfunctionofthemeis332shugoshin AT orrweaverterryl drosophilaproteinphosphatases2abwdbandwrdregulatemeioticcentromerelocalizationandfunctionofthemeis332shugoshin |