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

Abstract

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.