Selective dephosphorylation by PP2A-B55 directs the meiosis I - meiosis II transition in oocytes

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 sea star oocytes from prophase I through the first embryonic cleavage. Although protein levels are broadly stable, 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 rewires the cell division apparatus to direct the MI / MII transition.

Regulation of oocyte maturation: Role of conserved ERK signaling

“…One possibility is the differential regulation of ERK activity. A recent study using a time-course proteomics approach tested the mechanisms regulating meiosis I-meiosis II transition in synchronized sea star oocytes (Swartz et al, 2021). The authors found that there is a differential regulation of serine and threonine dephosphorylation during the meiosis I-meiosis II transition.…”

“…The authors found that there is a differential regulation of serine and threonine dephosphorylation during the meiosis I-meiosis II transition. Protein phosphatase PP2A-B55 preferentially dephosphorylates threonine residues and thus temporally regulates the activity of its substrates, including CDK and ERK (Swartz et al, 2021). Another possibility is the involvement of other signaling regulators, such as CDK1 or PLK1, which along with ERK, control specific subsets of substrates during the meiosis I-meiosis II transition.…”

Inducible protein degradation as a strategy to identify Phosphoprotein Phosphatase 6 substrates in RAS-mutant colorectal cancer cells

“…The sAID was fused to the N-terminus of PPP6c to ensure tagging of the three annotated alternative splice isoforms of PPP6c, and to avoid interference with C-terminal methylation. For proteomic and phosphoproteomic analyses of untreated and auxin (IAA) treated cells, three or four biological replicates were generated and analyzed using our established and reproducible workflow (13, 55, 56). For the proteomic study, 40 μg of peptides were removed from the trypsin digest of each condition.…”

“…For proteomic and phosphoproteomic analyses of untreated and auxin (IAA) treated cells, three or four biological replicates were generated and analyzed using our established and reproducible workflow (13,55,56). For the proteomic study, 40 μg of peptides were removed from the trypsin digest of each condition.…”