Defining Akt actions in muscle differentiation

Samantha Gardner, Magdalena Anguiano, Peter Rotwein

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration. Here we find that of the two Akts expressed in muscle, Akt1 is essential for initiation of differentiation in culture and is required for normal myoblast motility, while Akt2 is dispensable. Although Akt2 deficiency did lead to diminished myotube maturation, as assessed by a decline in myofiber area and in fusion index, either Akt1 or Akt2 could restore these processes toward normal. Thus levels of Akt expression rather than distinct actions of individual Akt species are critical for normal myofiber development during the later stages of muscle differentiation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume303
Issue number12
DOIs
StatePublished - Dec 15 2012

Fingerprint

Muscles
Muscle Development
Regeneration
Phosphatidylinositol 3-Kinase
Myoblasts
Skeletal Muscle Fibers
Wounds and Injuries
Muscle Strength
Somatomedins
Growth Hormone
Intercellular Signaling Peptides and Proteins
Transcription Factors
Phosphotransferases
Stem Cells
Growth

Keywords

  • Akt1
  • Akt2
  • Myofiber fusion
  • Skeletal muscle differentiation

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Defining Akt actions in muscle differentiation. / Gardner, Samantha; Anguiano, Magdalena; Rotwein, Peter.

In: American Journal of Physiology - Cell Physiology, Vol. 303, No. 12, 15.12.2012.

Research output: Contribution to journalArticle

Gardner, Samantha ; Anguiano, Magdalena ; Rotwein, Peter. / Defining Akt actions in muscle differentiation. In: American Journal of Physiology - Cell Physiology. 2012 ; Vol. 303, No. 12.
@article{6c80e6d6ef09419ca0065899724b726c,
title = "Defining Akt actions in muscle differentiation",
abstract = "Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration. Here we find that of the two Akts expressed in muscle, Akt1 is essential for initiation of differentiation in culture and is required for normal myoblast motility, while Akt2 is dispensable. Although Akt2 deficiency did lead to diminished myotube maturation, as assessed by a decline in myofiber area and in fusion index, either Akt1 or Akt2 could restore these processes toward normal. Thus levels of Akt expression rather than distinct actions of individual Akt species are critical for normal myofiber development during the later stages of muscle differentiation.",
keywords = "Akt1, Akt2, Myofiber fusion, Skeletal muscle differentiation",
author = "Samantha Gardner and Magdalena Anguiano and Peter Rotwein",
year = "2012",
month = "12",
day = "15",
doi = "10.1152/ajpcell.00259.2012",
language = "English (US)",
volume = "303",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "12",

}

TY - JOUR

T1 - Defining Akt actions in muscle differentiation

AU - Gardner, Samantha

AU - Anguiano, Magdalena

AU - Rotwein, Peter

PY - 2012/12/15

Y1 - 2012/12/15

N2 - Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration. Here we find that of the two Akts expressed in muscle, Akt1 is essential for initiation of differentiation in culture and is required for normal myoblast motility, while Akt2 is dispensable. Although Akt2 deficiency did lead to diminished myotube maturation, as assessed by a decline in myofiber area and in fusion index, either Akt1 or Akt2 could restore these processes toward normal. Thus levels of Akt expression rather than distinct actions of individual Akt species are critical for normal myofiber development during the later stages of muscle differentiation.

AB - Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration. Here we find that of the two Akts expressed in muscle, Akt1 is essential for initiation of differentiation in culture and is required for normal myoblast motility, while Akt2 is dispensable. Although Akt2 deficiency did lead to diminished myotube maturation, as assessed by a decline in myofiber area and in fusion index, either Akt1 or Akt2 could restore these processes toward normal. Thus levels of Akt expression rather than distinct actions of individual Akt species are critical for normal myofiber development during the later stages of muscle differentiation.

KW - Akt1

KW - Akt2

KW - Myofiber fusion

KW - Skeletal muscle differentiation

UR - http://www.scopus.com/inward/record.url?scp=84871319553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871319553&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00259.2012

DO - 10.1152/ajpcell.00259.2012

M3 - Article

VL - 303

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 12

ER -