CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
EIF4E AND 4E-BP MODULATES CALCIUM HANDLING IN DROSOPHILA HEART THROUGH DIRECT INTERACTION BETWEEN EIF4E-4 AND SERCA PUMP
VALVERDE CA; MATTIAZZI A; SANTALLA M; FERRERO P; GARCÍA A
Congreso; Reunión Conjunta De Sociedades De Biociencias.; 2017
We studied the effect of genetic up and downregulation of eIF4E and 4E-BP on cardiac calcium handling using Drosophila melanogaster as genetic model. We assessed the intracellular calcium level by registering the fluorescent signal of a cardiac reporter system (TinC-Gal4-UAS-GCaMP3) in semi-intact preparation of 7 days-old flies. Overexpression of 4E-BP incremented the Ca2+-transient amplitude and relaxation, and the sarcoplasmic reticulum (SR) calcium load. These effects were linked to a higher SR Ca2+ reuptake through the Ca+2-ATPase pump (SERCA). Therefore, the release of Ca2+ by ryanodine receptors (RyR) was higher than control. In particular, the activity of SERCA was modified in our transgenic lines of flies that have overexpressed 4EBP.Through bioinformatic analysis we found that SERCA possesses within its amino acid sequence the domain of interaction with eIF4E present in 4EBP (YXXXXLφ) which would suggest that the results observed by the functional experiments could be due to an interaction between the eIF4E and SERCA proteins, affected Ppobably by 4E-BP, whose eIF4E binding site is the same as that of SERCA.Using a double hybrid assay we assessed the interaction of the seven isoforms of Drosophila's eIF4E with SERCA . We found that only eIF4E-4 interacts directly with SERCA. This results suggest that the effects in the activity of SERCA observed in the transgenics lines could be due to the direct interaction probed between SERCA and eIF4E-4.Our results provide evidence of the effects of modulating 4EBP in the heart of drosophila and that these effects may be due to an interaction between the protein regulated by 4EBP, eIF4E, more precisely its isoform 4 and SERCA.