title: Gαi2 signaling is required for skeletal muscle growth, regeneration, and satellite cell proliferation and differentiation.
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.
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1, Novartis Campus, Basel, Switzerland.
authors.forename: Giulia C
authors.initials: GC
authors.lastname: Minetti
authors.forename: Jerome N
authors.initials: JN
authors.lastname: Feige
authors.forename: Florian
authors.initials: F
authors.lastname: Bombard
authors.forename: Annabelle
authors.initials: A
authors.lastname: Heier
authors.forename: Fredric
authors.initials: F
authors.lastname: Morvan
authors.forename: Bernd
authors.initials: B
authors.lastname: Nürnberg
authors.forename: Veronika
authors.initials: V
authors.lastname: Leiss
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.forename: Mara
authors.initials: M
authors.lastname: Fornaro
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics* / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D051960:GTP-Binding Protein alpha Subunit, Gi2