Modelization of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive.
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 (koff1) of the eIF4E: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 eIF4E:eIF4G 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 eIF4E: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.
Ifremer, UMR6197, Laboratoire de Microbiologie des Environnements Extrêmes Plouzané, France.
Sébastien
S
Laurent
Université de Nice-Sophia Antipolis, UMR 7271, Laboratoire I3S Sophia, Antipolis, France.
Adrien
A
Richard
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Odile
O
Mulner-Lorillon
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Julia
J
Morales
Ifremer, UMR6197, Laboratoire de Microbiologie des Environnements Extrêmes Plouzané, France.
Didier
D
Flament
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Virginie
V
Glippa
CNRS UMR 6241, Laboratoire LINA, Université de Nantes Nantes, France.
Jérémie
J
Bourdon
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Pauline
P
Gosselin
CNRS, IRISA-UMR 6074, Campus de Beaulieu Rennes, France ; INRIA, Centre Rennes - Bretagne Atlantique, Symbiose, Campus de Beaulieu Rennes, France.
Anne
A
Siegel
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Patrick
P
Cormier
Sorbonne Universités, UPMC University Paris 06, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France ; CNRS, UMR 8227, Integrative Biology of Marine Models, Translation Cell Cycle and Development Station Biologique de Roscoff, Roscoff cedex, France.
Robert
R
Bellé
deterministic model; mechanisms of fertilization; sea urchin embryos; translation simulation; translational control