Knockdown of the cAMP-dependent protein kinase (PKA) type Iα regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects

Francesca E. Duncan, Stuart B. Moss, Carmen J. Williams*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

In mammalian oocytes, cyclic AMP-dependent protein kinase (PKA) is responsible for maintaining meiotic arrest. We examined the role of the predominant regulatory subunit, RIα in regulating PKA activity during mouse oocyte maturation by knocking down the protein levels using an RNA interference approach. In oocytes in which RIα protein was reduced to non-detectable levels, compensatory decreases were also observed in the RIIα and catalytic (Cα) subunit levels. These oocytes resumed meiosis, despite culture under conditions that maintain elevated intracellular cAMP levels, suggesting that the remaining Cα was not sufficient to maintain meiotic arrest. The resulting eggs, however, displayed meiotic spindle abnormalities and abnormal cleavage planes leading to extrusion of large polar bodies. These results demonstrate that RIα is required for regulating PKA activity in maturing oocytes and that compensatory upregulation of RII does not occur. Furthermore, we implicate PKA as a modulator of spindle morphology and function during meiosis.

Original languageEnglish (US)
Pages (from-to)2961-2968
Number of pages8
JournalDevelopmental Dynamics
Volume235
Issue number11
DOIs
StatePublished - Nov 2006

Keywords

  • Meiosis
  • Mouse oocyte
  • Protein kinase A
  • RNAi
  • Spindle

ASJC Scopus subject areas

  • Developmental Biology

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