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bioRxiv · 10.1101/2025.10.03.680315

Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events

Roque, S.·Hassen Khodja, C.·Ben Choug, C.·Vigneron, S.·Legros, V.·Chevreux, G.·Lacroix, B.·Castro, A.·Lorca, T.
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Abstract

Meiotic progression relies on maintaining a precise balance between cyclin B/CDK1 activity and the phosphatase PP2A-B55. The latter is negatively regulated by the Greatwall kinase (Gwl). In Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 severely disrupt the transition from meiosis I to meiosis II. This disruption prevents phosphorylation of both Wee1/Myt1 and the APC/C complex, thereby blocking APC/C activation. As a consequence, APC/C remains inactive during the MI-MII transition, which impairs cyclin degradation and the partial CDK1 inactivation that is normally required at this stage. Additionally, the mos-MAPK-Rsk1/2 pathway fails to activate due to insufficient Mos accumulation, thereby preventing metaphase II arrest. Finally, the lack of APC/C activation during meiosis I inhibits the degradation of its inhibitor Erp1, revealing a critical feedback loop between APC/C and Erp1. Overall, our findings reveal that Gwl is a key coordinator of both meiotic divisions, acting through dual regulation of APC/C and the Mos/MAPK/Rsk1/2 pathways by modulating PP2A-B55 activity.

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Roque, S., Hassen Khodja, C., Ben Choug, C., Vigneron, S., Legros, V., Chevreux, G., Lacroix, B., Castro, A., Lorca, T.. 2025-10-04. Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events. https://doi.org/10.1101/2025.10.03.680315

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