Selective dephosphorylation by PP2A-B55 directs the meiosis I - meiosis II transition in oocytes
- Massachusetts Institute of Technology, United States
- Geisel School of Medicine at Dartmouth, United States
- Whitehead Institute, United States
Abstract
Meiosis is a specialized cell cycle that requires sequential changes to the cell division machinery to facilitate changing functions. To define the mechanisms that enable the oocyte-to-embryo transition, we performed time-course proteomics in synchronized sea star oocytes from prophase I through the first embryonic cleavage. Although we find that protein levels are broadly stable, our analysis reveals that dynamic waves of phosphorylation underlie each meiotic stage. We find that the phosphatase PP2A-B55 is reactivated at the meiosis I/II transition resulting in the preferential dephosphorylation of threonine residues. Selective dephosphorylation is critical for directing the MI / MII transition as altering PP2A-B55 substrate preferences disrupts key cell cycle events after meiosis I. In addition, threonine to serine substitution of a conserved phosphorylation site in the substrate INCENP prevents its relocalization at anaphase I. Thus, through its inherent phospho-threonine preference, PP2A-B55 imposes specific phosphoregulated behaviors that distinguish the two meiotic divisions.
Data availability
Raw MS data for the experiments performed in this study are available at MassIVE and ProteomeXchange, accession number: PXD020916, password: p845. Plasmids generated from this study are deposited to Addgene. Custom R script is available at Github.
Article and author information
Author details
Arminja N Kettenbach
Funding
National Institute of General Medical Sciences (R35GM126930)
- Iain M Cheeseman
National Institute of General Medical Sciences (R35GM119455)
- Arminja N Kettenbach
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD099315)
- S Zachary Swartz
Gordon and Betty Moore Foundation
- Iain M Cheeseman
Global Consortium for Reproductive Longevity and Equity (GCRLE-1220)
- Iain M Cheeseman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jon Pines, Institute of Cancer Research Research, United Kingdom
Version history
- Preprint posted: August 21, 2020 (view preprint)
- Received: May 23, 2021
- Accepted: August 2, 2021
- Accepted Manuscript published: August 3, 2021 (version 1)
- Version of Record published: August 17, 2021 (version 2)
Copyright
© 2021, Swartz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Selective dephosphorylation by PP2A-B55 directs the meiosis I - meiosis II transition in oocytes
eLife 10:e70588.
https://doi.org/10.7554/eLife.70588
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