| First Author | Minetti GC | Year | 2011 |
| Journal | Sci Signal | Volume | 4 |
| Issue | 201 | Pages | ra80 |
| PubMed ID | 22126963 | Mgi Jnum | J:259488 |
| Mgi Id | MGI:6141290 | Doi | 10.1126/scisignal.2002038 |
| Citation | Minetti GC, et al. (2011) Galphai2 signaling promotes skeletal muscle hypertrophy, myoblast differentiation, and muscle regeneration. Sci Signal 4(201):ra80 |
| abstractText | Skeletal muscle atrophy results in loss of strength and an increased risk of mortality. We found that lysophosphatidic acid, which activates a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor, stimulated skeletal muscle hypertrophy through activation of Galpha(i2). Expression of a constitutively active mutant of Galpha(i2) stimulated myotube growth and differentiation, effects that required the transcription factor NFAT (nuclear factor of activated T cells) and protein kinase C. In addition, expression of the constitutively active Galpha(i2) mutant inhibited atrophy caused by the cachectic cytokine TNFalpha (tumor necrosis factor-alpha) by blocking an increase in the abundance of the mRNA encoding the E3 ubiquitin ligase MuRF1 (muscle ring finger 1). Galpha(i2) activation also enhanced muscle regeneration and caused a switch to oxidative fibers. Our study thus identifies a pathway that promotes skeletal muscle hypertrophy and differentiation and demonstrates that Galpha(i2)-induced signaling can act as a counterbalance to MuRF1-mediated atrophy, indicating that receptors that act through Galpha(i2) might represent potential targets for preventing skeletal muscle wasting. |
