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 found that protein levels were broadly stable, our analysis reveals that dynamic waves of phosphorylation underlie each meiotic stage. We found that the phosphatase PP2A-B55 is reactivated at the meiosis I/meiosis II (MI/MII) 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 MI. 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.
Highlights
Animal reproduction requires that oocytes undergo a specialized cell cycle called meiosis, in which two functionally distinct divisions occur in rapid succession to reduce genome ploidy (Kishimoto, 2018a)
We propose a model in which the usage of threonine versus serine endows substrates with different responsivity to a common set of kinases and phosphatases, temporally coordinating individual proteins with meiotic cell cycle progression to achieve specific behaviors for meiosis I (MI) and meiosis II (MII) without exiting from meiosis
Based on a proteomic analysis of meiosis II and pronuclear stage 146 oocytes, we found that only 108 out of 7,610 proteins identified in our analysis significantly changed with emetine treatment (Figure 2—figure supplement 1, supplementary file 3)
Summary
Animal reproduction requires that oocytes undergo a specialized cell cycle called meiosis, in which two functionally distinct divisions occur in rapid succession to reduce genome ploidy (Kishimoto, 2018a). An important goal is to unravel the complex regulatory mechanisms that precisely coordinate these divisions in time and space within the oocyte It remains unknown how phosphorylation and dephosphorylation drive the meiotic divisions allowing oocytes to rewire the cell division machinery at the meiosis I/II transition to facilitate differing requirements. We identify a surprising differential behavior between serine and threonine dephosphorylation at the MI/MII transition that we propose underlies key regulatory differences between these meiotic divisions This regulatory switch is driven by PP2A-B55, which is reactivated after MI to preferentially dephosphorylate threonine residues, thereby creating temporally distinct reversals of cyclin-dependent kinase and MAP kinase phosphorylation. We propose a model in which the usage of threonine versus serine endows substrates with different responsivity to a common set of kinases and phosphatases, temporally coordinating individual proteins with meiotic cell cycle progression to achieve specific behaviors for MI and MII without exiting from meiosis
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