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 maturing Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 prevents phosphorylation of key proteins involved in spindle formation, chromosome condensation and spindle migration as well as the phosphorylation of Wee1/Myt1 and the APC/C complex. As a consequence, in these oocytes bipolar spindles cannot be formed and migrate to the cortex and chromosomes are partially decondensed preventing meiotic I progression. The APC/C remains inactive impairing cyclin B3 degradation and ultimately preventing Erp1 accumulation. Finally, the c-Mos-MAPK-Rsk1/2 pathway fails to activate due to the absence of c-Mos as a consequence of its improper degradation. Overall, our findings reveal a crucial role of Gwl in the coordination and progression of meiotic divisions.
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Acknowledgements
We would like to thank Marc Plays and Anthony Ollier for providing the Xenopus females, the ZEFIX animal facility, and for immunising the rabbits and recovering the antibodies. APC1 phospho-antibodies were a generous gift from the laboratory of Hiro Yamano, University College of London, UK. TRIM21 cDNA was kindly provided by Sebastian Nisole, IRIM, Montpellier. We acknowledge the imaging facility MRI, member of the national infrastructure France-BioImaging (https://ror.org/01y7vt929) supported by the French National Research Agency (ANR-24-INBS-0005 FBI BIOGEN). The work in the laboratory is supported by grants from the Agence Nationale pour la Recherche (ANR, France – ANR-22-CE13-0022 (TL), ANR-23-CE18-0050 (AC), and ANR-20-CE13-0033 (BL)), Université de Montpellier,” Accelerateur Innovation” 2022 (NewObTrea) (AC), and the Fondation ARC pour la Recherche sur le Cancer (PJA3 TL ARCPJA2023060006673).
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Roque, S., Ben Choug, C., Khodja, C.H. et al. Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73011-5
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DOI: https://doi.org/10.1038/s41467-026-73011-5
