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
C2 - 23076793
AN - SCOPUS:84871319553
SN - 0363-6143
VL - 303
SP - C1292-C1300
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 12
ER -