Distinct actions of Akt1 and Akt2 in skeletal muscle differentiation

Peter Rotwein, Elizabeth M. Wilson

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Differentiation, maturation, and repair of skeletal muscle requires ongoing cooperation between signaling cascades activated by hormones and growth factors, and intrinsic regulatory programs controlled by myogenic transcription factors. The insulin-like growth factor - phosphatidylinositol-3 kinase - Akt pathway has been implicated in muscle growth and regeneration after injury, in counteracting sarcopenia during aging, and in maintaining muscle cell viability. Here we present evidence for distinct roles for Akt1 and Akt2 in different phases of muscle differentiation. Targeted knockdown of either Akt had no effect on C2 myoblast proliferation, even though Akt1 concentrations are markedly higher than Akt2 levels under growth-promoting conditions. Akt2 concentrations rose by nearly an order of magnitude during muscle differentiation, while Akt1 levels remained constant, yet loss of either protein did not increase myoblast death. Rather, knockdown or genetic knockout of Akt1 blocked differentiation at its earliest stages, preventing induction of muscle-specific proteins and inhibiting formation of multinucleated myofibers, while myoblasts lacking Akt2 differentiated normally, although resultant myofibers were thinner and incorporated fewer nuclei than controls. Forced expression of knockdown-resistant Akt1 partially reversed the deficit in differentiation seen in myoblasts lacking Akt1. Our results define isoform-specific Akt actions in muscle cells, and demonstrate that both Akts are necessary for full myoblast differentiation and maturation.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
JournalJournal of Cellular Physiology
Volume219
Issue number2
DOIs
StatePublished - May 2009

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Myoblasts
Muscle
Skeletal Muscle
Muscles
Muscle Cells
Phosphatidylinositol 3-Kinase
Sarcopenia
Muscle Proteins
Somatomedins
Cells
Growth
Regeneration
Cell Survival
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Transcription Factors
Hormones
Proteins
Repair
Wounds and Injuries

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Distinct actions of Akt1 and Akt2 in skeletal muscle differentiation. / Rotwein, Peter; Wilson, Elizabeth M.

In: Journal of Cellular Physiology, Vol. 219, No. 2, 05.2009, p. 503-511.

Research output: Contribution to journalArticle

Rotwein, Peter ; Wilson, Elizabeth M. / Distinct actions of Akt1 and Akt2 in skeletal muscle differentiation. In: Journal of Cellular Physiology. 2009 ; Vol. 219, No. 2. pp. 503-511.
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