Female infertility in PDE3A(-/-) mice: polo-like kinase 1 (Plk1) may be a target of protein kinase A (PKA) and involved in meiotic arrest of oocytes from PDE3A(-/-) mice

Cell Cycle. 2010 Dec 1;9(23):4720-34. doi: 10.4161/cc.9.23.14090. Epub 2010 Dec 1.

Abstract

Mechanisms of cAMP/PKA-induced meiotic arrest in oocytes are not completely identified. In cultured, G2/M-arrested PDE3A(-/-) murine oocytes, elevated PKA activity was associated with inactivation of Cdc2 and Plk1, and inhibition of phosphorylation of histone H3 (S10) and of dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15). In cultured WT oocytes, PKA activity was transiently reduced and then increased to that observed in PDE3A(-/-) oocytes; Cdc2 and Plk1 were activated, phosphorylation of histone H3 (S10) and dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15) were observed. In WT oocytes, PKAc were rapidly translocated into nucleus, and then to the spindle apparatus, but in PDE3A(-/-) oocytes, PKAc remained in the cytosol. Plk1 was reactivated by incubation of PDE3A(-/-) oocytes with PKA inhibitor, Rp-cAMPS. PDE3A was co-localized with Plk1 in WT oocytes, and co-immunoprecipitated with Plk1 in WT ovary and Hela cells. PKAc phosphorylated rPlk1 and Hela cell Plk1 and inhibited Plk1 activity in vitro. Our results suggest that PKA-induced inhibition of Plk1 may be critical in oocyte meiotic arrest and female infertility in PDE3A(-/-) mice.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CDC2 Protein Kinase / analysis
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cell Division
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / analysis
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism*
  • Cyclin B1 / metabolism
  • Female
  • G2 Phase
  • Genotype
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Infertility, Female / enzymology*
  • Infertility, Female / metabolism
  • Meiosis
  • Mice
  • Mice, Knockout
  • Oocytes / enzymology*
  • Oocytes / growth & development
  • Oocytes / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • cdc25 Phosphatases / metabolism

Substances

  • Cell Cycle Proteins
  • Cyclin B1
  • Histones
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Cyclic AMP-Dependent Protein Kinases
  • CDC2 Protein Kinase
  • Cdc25b protein, mouse
  • cdc25 Phosphatases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Pde3a protein, mouse