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Updated: Jul 3, 2025

Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Unraveling the interplay between PKA inhibition and Cdk1 activation during oocyte meiotic maturation
Martina Santoni1, Ferdinand Meneau1, Nabil Sekhsoukh1
1Sorbonne Université-CNRS, Laboratoire de Biologie du Développement Institut de Biologie Paris Seine, LBD-IBPS, 75005 Paris, France.
Abstract:
Oocytes are arrested in prophase I. In vertebrates, meiotic resumption is triggered by hormonal stimulation that results in cAMP-dependent protein kinase (PKA) downregulation leading to Cdk1 activation. Yet the pathways connecting PKA to Cdk1 remain unclear. Here, we identify molecular events triggered by PKA downregulation occurring upstream of Cdk1 activation. We describe a two-step regulation controlling cyclin B1 and Mos accumulation, which depends on both translation and stabilization. Cyclin B1 accumulation is triggered by PKA inhibition upstream of Cdk1 activation, while its translation requires Cdk1 activity. Conversely, Mos translation initiates in response to the hormone, but the protein accumulates only downstream of Cdk1. Furthermore, two successive translation waves take place, the first controlled by PKA inhibition and the second by Cdk1 activation. Notably, Arpp19, an essential PKA effector, does not regulate the early PKA-dependent events. This study elucidates how PKA downregulation orchestrates multiple pathways that converge toward Cdk1 activation and induce the oocyte G2/M transition.
Insights
Hormonal stimulation triggers oocyte maturation by downregulating protein kinase A (PKA), leading to Cdk1 activation. This study reveals how PKA inhibition orchestrates cyclin B1 and Mos accumulation, driving the G2/M transition.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Reproductive Biology
Background:
- Oocytes arrest in prophase I, requiring hormonal signals for meiotic resumption.
- Hormonal stimulation leads to protein kinase A (PKA) downregulation and cyclin-dependent kinase 1 (Cdk1) activation.
- The precise molecular pathways linking PKA to Cdk1 activation remain incompletely understood.
Purpose of the Study:
- To identify molecular events upstream of Cdk1 activation that are triggered by PKA downregulation.
- To elucidate the regulation of cyclin B1 and Mos accumulation during meiotic resumption.
- To understand the sequential control of translation waves during the oocyte G2/M transition.
Main Methods:
- Analysis of cyclin B1 and Mos protein accumulation.
- Investigation of translational and stabilization mechanisms.
- Assessment of PKA and Cdk1 activities during meiotic resumption.
- Evaluation of the role of Arpp19 in PKA-dependent events.
Main Results:
- PKA inhibition, upstream of Cdk1 activation, triggers cyclin B1 accumulation.
- Cyclin B1 translation requires Cdk1 activity, while Mos translation initiates upon hormonal stimulation but accumulates post-Cdk1 activation.
- Two distinct translation waves occur: the first PKA-dependent, the second Cdk1-dependent.
- Arpp19, a PKA effector, does not influence early PKA-dependent events.
Conclusions:
- PKA downregulation orchestrates a multi-step process involving translation and stabilization of key proteins.
- These pathways converge to activate Cdk1, driving the oocyte G2/M transition and meiotic resumption.
- The findings clarify the regulatory network connecting PKA and Cdk1 in oocyte maturation.
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