Paxillin regulates steroid-triggered meiotic resumption in oocytes by enhancing an all-or-none positive feedback

Melissa Rasar1, Donald B DeFranco, Stephen R Hammes

  • 1Department of Internal Medicine, Division of Endocrinology and Metabolism, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-8857, USA.

Insights

Paxillin is a newly identified regulator of oocyte maturation, essential for steroid-triggered meiotic resumption in Xenopus. This scaffold molecule modulates the positive feedback kinase cascade involving MOS, MEK1, and ERK2 signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Reproductive Biology

Background:

  • Oocyte maturation is initiated by steroids via a transcription-independent pathway.
  • This process involves a positive feedback loop where MOS activates MEK1, which activates ERK2, further enhancing MOS expression.

Purpose of the Study:

  • To identify novel regulators of the MOS-MEK1-ERK2 positive feedback kinase cascade.
  • To investigate the role of the scaffold molecule Paxillin in Xenopus laevis oocyte maturation.

Main Methods:

  • RNA interference and antisense oligonucleotides were used to reduce Paxillin expression.
  • Signaling studies were conducted to analyze the effects of Paxillin on the kinase cascade.
  • Serine phosphorylation of Paxillin was assessed.

Main Results:

  • Paxillin is essential for steroid-induced meiotic resumption in Xenopus oocytes.
  • Paxillin is required for MOS protein accumulation and activation of downstream kinases.
  • Paxillin activity is regulated by serine phosphorylation, potentially by ERK2.

Conclusions:

  • Paxillin is a critical regulator of the positive feedback loop in oocyte maturation.
  • Paxillin modulates MEK/ERK signaling and MOS protein expression.
  • Paxillin may serve as a general modulator of mitogen-activated protein kinase signaling pathways.

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