Modelization of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of elF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive
|Author(s)||Laurent Sebastien1, Richard Adrien2, Mulner-Lorillon Odile3, 4, Morales Julia3, 4, Flament Didier1, Glippa Virginie3, 4, Bourdon Jeremie5, Gosselin Pauline3, 4, Siegel Anne6, 7, Cormier Patrick3, 4, Belle Robert3, 4|
|Affiliation(s)||1 : IFREMER, Lab Microbiol Environm Extremes, UMR6197, Plouzane, France.
2 : Univ Nice Sophia Antipolis, Lab I3S, UMR 7271, Sophia, Antipolis, France.
3 : UPMC, Univ Sorbonne, UMR 8227, Stn Biol Roscoff, F-29688 Roscoff, France.
4 : CNRS, UMR 8227, Stn Biol Roscoff, F-29688 Roscoff, France.
5 : Univ Nantes, CNRS, Lab LINA, UMR 6241, Nantes, France.
6 : CNRS, IRISA, UMR 6074, Rennes, France.
7 : INRIA, Ctr Rennes Bretagne Atlantic, Rennes, France.
|Source||Frontiers In Genetics (1664-8021) (Frontiers Media Sa), 2014-05 , Vol. 5 , N. 117 , P. 1-10|
|WOS© Times Cited||5|
|Keyword(s)||translational control, sea urchin embryos, mechanisms of fertilization, deterministic model, translation simulation|
Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in the total 4E-BP amount observed during time after fertilization. Our study evidenced that two changes occurring at fertilization are necessary to fit with experimental data. The first change was an 8-fold increase in the dissociation parameter (koffi) of the elF4E:4E-BP complex. The second was an important 32.5-fold activation of the degradation mechanism of the protein 4E-BP Additionally, the changes in both processes should occur in 5 min time interval post-fertilization. To validate the model, we checked that the kinetic of the predicted 4.2-fold increase of elF4E:e1F4G complex concentration at fertilization matched the increase of protein synthesis experimentally observed after fertilization (6.6-fold, SD = 2.3, n = 8). The minimal model was also used to simulate changes observed after fertilization in the presence of rapamycin, a FRAP/mTOR inhibitor. The model showed that the elF4E:4E-BP complex destabilization was impacted and surprisingly, that the mechanism of 4E-BP degradation was also strongly affected, therefore suggesting that both processes are controlled by the protein kinase FRAP/mTOR.