Title | Phosphorylation of eukaryotic initiation factor 4E is dispensable for skeletal muscle hypertrophy. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Figueiredo VC, Englund DA, Vechetti IJ, Alimov A, Peterson CA, McCarthy JJ |
Journal | Am J Physiol Cell Physiol |
Volume | 317 |
Issue | 6 |
Pagination | C1247-C1255 |
Date Published | 2019 12 01 |
ISSN | 1522-1563 |
Keywords | Animals, Biomechanical Phenomena, Cyclin D1, Eukaryotic Initiation Factor-4E, Female, Gene Expression Regulation, Gene Knock-In Techniques, Hypertrophy, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal, Nuclear Proteins, Organelle Biogenesis, Phosphorylation, Protein Biosynthesis, Proto-Oncogene Proteins c-myc, Ribosomes, RNA, Ribosomal, Serine, Signal Transduction |
Abstract | The eukaryotic initiation factor 4E (eIF4E) is a major mRNA cap-binding protein that has a central role in translation initiation. Ser 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 Ser promotes translation of key mRNAs, such as cyclin D1, that regulate ribosome biogenesis. We hypothesized that phosphorylation at Ser 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, Ser 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 Ser is dispensable for skeletal muscle hypertrophy in response to mechanical overload. |
DOI | 10.1152/ajpcell.00380.2019 |
Alternate Journal | Am. J. Physiol., Cell Physiol. |
PubMed ID | 31596607 |
PubMed Central ID | PMC6962521 |
Grant List | TL1 TR001997 / TR / NCATS NIH HHS / United States |