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

Type Article
Date 2014-05
Language English
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
DOI 10.3389/fgene.2014.00117
WOS© Times Cited 5
Keyword(s) translational control, sea urchin embryos, mechanisms of fertilization, deterministic model, translation simulation
Abstract

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.

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Laurent Sebastien, Richard Adrien, Mulner-Lorillon Odile, Morales Julia, Flament Didier, Glippa Virginie, Bourdon Jeremie, Gosselin Pauline, Siegel Anne, Cormier Patrick, Belle Robert (2014). 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. Frontiers In Genetics, 5(117), 1-10. Publisher's official version : https://doi.org/10.3389/fgene.2014.00117 , Open Access version : https://archimer.ifremer.fr/doc/00382/49341/