Phosphorylation of eukaryotic initiation factor 4E is dispensable for skeletal muscle hypertrophy

Vandre C. Figueiredo, Davis A. Englund, Ivan J. Vechetti, Alexander Alimov, Charlotte A. Peterson, John J. McCarthy

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The eukaryotic initiation factor 4E (eIF4E) is a major mRNA cap-binding protein that has a central role in translation initiation. Ser209 is the single phosphorylation site within eIF4E and modulates its activity in response to MAPK pathway activation. It has been reported that phosphorylation of eIF4E at Ser209 promotes translation of key mRNAs, such as cyclin D1, that regulate ribosome biogenesis. We hypothesized that phosphorylation at Ser209 is required for skeletal muscle growth in response to a hypertrophic stimulus by promoting ribosome biogenesis. To test this hypothesis, wild-type (WT) and eIF4E knocked-in (KI) mice were subjected to synergist ablation to induce muscle hypertrophy of the plantaris muscle as the result of mechanical overload; in the KI mouse, Ser209 of eIF4E was replaced with a nonphosphorylatable alanine. Contrary to our hypothesis, we observed no difference in the magnitude of hypertrophy between WT and KI groups in response to 14 days of mechanical overload induced by synergist ablation. Similarly, the increases in cyclin D1 protein levels, ribosome biogenesis, and translational capacity did not differ between WT and KI groups. Based on these findings, we conclude that phosphorylation of eIF4E at Ser209 is dispensable for skeletal muscle hypertrophy in response to mechanical overload.

Original languageEnglish
Pages (from-to)C1247-C1255
JournalAmerican Journal of Physiology - Cell Physiology
Volume317
Issue number6
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 the American Physiological Society.

Keywords

  • Protein synthesis
  • Ribosome biogenesis
  • Skeletal muscle growth
  • Translation

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Phosphorylation of eukaryotic initiation factor 4E is dispensable for skeletal muscle hypertrophy'. Together they form a unique fingerprint.

Cite this