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Published on: September 27, 2015
GCN2 activation and eIF2alpha phosphorylation in the maturation of mouse oocytes
Viviane S Alves1, Fabiana L Motta, Martín Roffé
1Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, 862 04023-062 São Paulo, SP, Brazil.
Abstract:
GCN2 is one of the four mammalian kinases that phosphorylate the alpha subunit of the translation initiation factor 2 (eIF2alpha) in a variety of stress situations, resulting in protein synthesis inhibition. GCN2 is involved in regulating metabolism, feeding behavior and memory in rodents. We show here that, relative to other cells, the beta isoform of the GCN2 transcript and the GCN2 protein are highly abundant in unfertilized mouse eggs. In addition, GCN2 in these cells is active, resulting in elevated levels of phosphorylated eIF2alpha. After fertilization, eIF2alpha phosphorylation decreases drastically. These results suggest that GCN2 mediated translational control may contribute to regulatory mechanisms operating during oocyte maturation.
Insights
The GCN2 kinase is highly active in unfertilized mouse eggs, phosphorylating eIF2alpha. This activity significantly decreases after fertilization, suggesting a role in oocyte maturation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Developmental Biology
Background:
- GCN2 is a mammalian kinase that regulates protein synthesis under stress.
- It phosphorylates the alpha subunit of the translation initiation factor 2 (eIF2alpha).
- GCN2 plays roles in metabolism, feeding behavior, and memory in rodents.
Purpose of the Study:
- To investigate the role and activity of GCN2 in unfertilized mouse eggs.
- To determine the changes in GCN2 activity and eIF2alpha phosphorylation upon fertilization.
Main Methods:
- Quantitative analysis of GCN2 transcript and protein levels.
- Assessment of GCN2 kinase activity.
- Measurement of phosphorylated eIF2alpha levels in oocytes before and after fertilization.
Main Results:
- The beta isoform of the GCN2 transcript and protein are highly abundant in unfertilized mouse eggs compared to other cells.
- GCN2 is active in unfertilized eggs, leading to elevated phosphorylated eIF2alpha levels.
- Fertilization causes a drastic decrease in eIF2alpha phosphorylation.
Conclusions:
- GCN2-mediated translational control is highly active in unfertilized mouse eggs.
- This activity is significantly reduced post-fertilization.
- GCN2 likely plays a crucial role in the regulatory mechanisms of oocyte maturation.
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