Regulation of YAP1 during oocyte maturation

Area of Science:

• Cell Biology
• Reproductive Biology
• Molecular Biology

Background:

• Yes-associated protein 1 (YAP1) is crucial for cell proliferation and differentiation, regulated by cell cycle proteins and the actin cytoskeleton.
• YAP1 has been observed on the mitotic spindle, but its function in oocyte maturation remains uncharacterized.

Purpose of the Study:

• To investigate the effect of a YAP1 inhibitor on mouse oocyte maturation.
• To explore the involvement of cell cycle regulators and actin polymerization modulators in YAP1 localization and phosphorylation during oocyte maturation.

Main Methods:

• Mouse oocytes were cultured in vitro with inhibitors targeting YAP1, CDK1, PP2A, and actin polymerization.
• Oocyte maturation, YAP1 localization (immunocytochemistry), and YAP1 phosphorylation (western blot) were assessed.

Main Results:

• Inhibiting YAP1 activity with verteporfin impaired oocyte maturation, causing arrest at metaphase I with abnormal spindle structures.
• YAP1 localized to the meiotic spindle and became phosphorylated at T119 during metaphase I.
• YAP1 phosphorylation at T119 was partly regulated by PP2A phosphatase and correlated with CDK1 activity, but not significantly affected by CDK1 inhibitors.

Conclusions:

• Phosphorylated YAP1 (pYAP1) at T119 is associated with cell cycle regulators CDK1 and PP2A, and the meiotic spindle, independent of actin polymerization changes.
• This study reveals a novel role for YAP1 in regulating meiotic spindle morphology during oocyte maturation.
• Targeting YAP1 activity could lead to improved in vitro maturation protocols for oocytes.