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.

Cell Reports
|February 15, 2024
PubMed

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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