Neuregulin-dependent protein synthesis in C2C12 myotubes and rat diaphragm muscle

Nathan J. Hellyer, Carlos Bernardo Mantilla, Eunice W. Park, Wen Zhi Zhan, Gary C Sieck

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The nerve-derived trophic factor neuregulin (NRG) is a prime candidate molecule for modulating muscle fiber growth. NRG regulates signal transduction in skeletal muscle through activation of ErbB receptors present at the neuromuscular junction. In this study, we hypothesize that NRG increases protein synthesis in maturing muscle via a phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. NRG signal transduction and its ability to stimulate protein synthesis (measured by incorporation of [3H]phenylalanine into the protein pool) were investigated in differentiated C2C 12 myotubes and rat diaphragm muscle (DIAm). In C2C 12 myotubes, NRG dose dependently increased phosphorylation of ErbB3 and recruitment of the p85 subunit of PI3K. NRG also increased phosphorylation of Akt, a downstream effector of PI3K. NRG treatment increased total protein synthesis by 35% compared with untreated control myotubes. This NRG-induced increase in Akt phosphorylation and protein synthesis was completely blocked by wortmannin, an inhibitor of PI3K but was unaffected by PD-98059, an inhibitor of MEK. In DIAm obtained from 3-day-old rat pups, Akt phosphorylation increased ∼30-fold with NRG treatment (vs. untreated DIAm). NRG treatment also significantly increased protein synthesis in the DIAm by 29% after 3 h of incubation with [3H]phenylalanine (vs. untreated DIAm). Pretreatment with wortmannin abolished the NRG-induced increase in protein synthesis, suggesting a critical role for PI3K in this response. The results of the present study support the hypothesis that nerve-derived NRG contributes to the regulation of skeletal muscle mass by increasing protein synthesis via activation of PI3K.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume291
Issue number5
DOIs
StatePublished - 2006

Fingerprint

Neuregulins
Skeletal Muscle Fibers
Diaphragms
Diaphragm
Muscle
Rats
Phosphatidylinositol 3-Kinase
Muscles
Phosphorylation
Proteins
Signal transduction
Phenylalanine
Signal Transduction
Skeletal Muscle
Chemical activation
Neuromuscular Junction
Mitogen-Activated Protein Kinase Kinases

Keywords

  • Akt
  • ErbB
  • Heregulin
  • Protein biosynthesis
  • Skeletal muscle

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Neuregulin-dependent protein synthesis in C2C12 myotubes and rat diaphragm muscle. / Hellyer, Nathan J.; Mantilla, Carlos Bernardo; Park, Eunice W.; Zhan, Wen Zhi; Sieck, Gary C.

In: American Journal of Physiology - Cell Physiology, Vol. 291, No. 5, 2006.

Research output: Contribution to journalArticle

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