Minetti, Giulia, feige, Jerome, Bombard, Florian, Heier, Annabelle, Morvan, Frederic, Nuerberg, Bernd, Leiss , Veronika, Birnbaumer, Lutz, Glass, David and Fornaro, Mara (2013) Gαi2 signaling is required for skeletal muscle growth, regeneration and satellite cell proliferation and differentiation. Mol Cell Biol.

Abstract

We have previously shown that activation of Gαi2, an α subunit of the heterotrimeric G protein complex, induces skeletal muscle hypertrophy and myoblast differentiation. To determine whether Gαi2 is required for skeletal muscle growth or regeneration, mice null for Gαi2 were analyzed. Gαi2 knockout mice display decreased lean body mass, reduced muscle size and impaired skeletal muscle regeneration after cardiotoxin-induced injury. shRNA-mediated knockdown of Gαi2 in satellite cells (SCs) leads to defective satellite cell proliferation, fusion and differentiation ex vivo. The impaired differentiation is consistent with the observation that the myogenic regulatory factors MyoD and Myf5 are down-regulated upon knockdown of Gαi2. Interestingly, the expression of miR-1, miR-27b and miR-206, three microRNAs that have been shown to regulate SC proliferation and differentiation, is increased by a constitutively active mutant of Gαi2 (Q205L) and counter-regulated by Gαi2 knockdown. As to mechanism, this study demonstrates that Gαi2(Q205L) regulates satellite cell differentiation into myotubes in a PKC and HDAC-dependent manner.

Item Type:	Article
Keywords:	muscle growth; muscle regeneration; satellite cells; G
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/10679