1. Gαi2 signaling is required for skeletal muscle growth, regeneration, and satellite cell proliferation and differentiation.
- Author
-
Minetti GC, Feige JN, Bombard F, Heier A, Morvan F, Nürnberg B, Leiss V, Birnbaumer L, Glass DJ, and Fornaro M
- Subjects
- Animals, Cell Differentiation physiology, Cells, Cultured, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Development physiology, Muscle, Skeletal cytology, Myoblasts cytology, Myoblasts metabolism, Satellite Cells, Skeletal Muscle pathology, Signal Transduction genetics, Signal Transduction physiology, Cell Differentiation genetics, Cell Proliferation, GTP-Binding Protein alpha Subunit, Gi2 genetics, Muscle Development genetics, Muscle, Skeletal metabolism, Regeneration genetics, Satellite Cells, Skeletal Muscle metabolism
- 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, Gαi2-null mice were analyzed. Gαi2 knockout mice display decreased lean body mass, reduced muscle size, and impaired skeletal muscle regeneration after cardiotoxin-induced injury. Short hairpin RNA (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 downregulated upon knockdown of Gαi2. Interestingly, the expression of microRNA 1 (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 [Gαi2(Q205L)] and counterregulated by Gαi2 knockdown. As for the mechanism, this study demonstrates that Gαi2(Q205L) regulates satellite cell differentiation into myotubes in a protein kinase C (PKC)- and histone deacetylase (HDAC)-dependent manner.
- Published
- 2014
- Full Text
- View/download PDF