Interplay between SERCA, 4E-BP, and eIF4E in the Drosophila heart

PLoS One. 2022 May 19;17(5):e0267156. doi: 10.1371/journal.pone.0267156. eCollection 2022.

Abstract

Appropriate cardiac performance depends on a tightly controlled handling of Ca2+ in a broad range of species, from invertebrates to mammals. The role of the Ca2+ ATPase, SERCA, in Ca2+ handling is pivotal, and its activity is regulated, inter alia, by interacting with distinct proteins. Herein, we give evidence that 4E binding protein (4E-BP) is a novel regulator of SERCA activity in Drosophila melanogaster during cardiac function. Flies over-expressing 4E-BP showed improved cardiac performance in young individuals associated with incremented SERCA activity. Moreover, we demonstrate that SERCA interacts with translation initiation factors eIF4E-1, eIF4E-2 and eIF4E-4 in a yeast two-hybrid assay. The specific identification of eIF4E-4 in cardiac tissue leads us to propose that the interaction of elF4E-4 with SERCA may be the basis of the cardiac effects observed in 4E-BP over-expressing flies associated with incremented SERCA activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carrier Proteins / metabolism
  • Drosophila melanogaster / metabolism
  • Drosophila* / metabolism
  • Eukaryotic Initiation Factor-4E* / metabolism
  • Mammals / metabolism
  • Phosphoproteins / metabolism
  • Protein Binding

Substances

  • Carrier Proteins
  • Eukaryotic Initiation Factor-4E
  • Phosphoproteins
  • Calcium

Grants and funding

This work was supported by PICT 2014-2549 ANPCyT and SIB 2015 to P.F, by PICT 2014-2524 and PIP 0350 to AM and by grants from the Deutsche Forschungsgemeinschaft to A.P. and H.M (SFB 944, Physiology and dynamics of cellular microcompartments). G.H. was supported by internal funding of the National Institute of Cancer (Instituto Nacional de Cancerología, INCan), Mexico. A National Council of Science and Technology (CONACyT) PhD fellowship was awarded to A.G. (Nr. 436200). A.G. is part of the Program on Biological Sciences, UNAM (Doctorado en Ciencias Biológicas de la Universidad Nacional Autónoma de México).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.