Cellular neuroscienceExpression of G protein β subunits in rat skeletal muscle after nerve injury: Implication in the regulation of neuregulin signaling

Tight regulation of gene transcription is critical in muscle development as well as during the formation and maintenance of the neuromuscular junction (NMJ). We previously demonstrated that the transcription of G protein β1 (Gβ1) is enhanced by treatment of cultured myotubes with neuregulin (NRG), a trophic factor that plays an important role in neural development. In the current study, we report that the transcript levels of Gβ1 and Gβ2 subunits in skeletal muscle are up-regulated following sciatic nerve injury or blockade of nerve activity. These observations prompted us to explore the possibility that G protein subunits regulate NRG-mediated signaling and gene transcription. We showed that overexpression of Gβ1 or Gβ2 in COS7 cells attenuates NRG-induced extracellular signal-regulated kinase (ERK) 1/2 activation, whereas suppression of Gβ2 expression in C2C12 myotubes enhances NRG-mediated ERK1/2 activation and c-fos transcription. These results suggest that expression of Gβ protein negatively regulates NRG-stimulated gene transcription in cultured myotubes. Taken together, our observations provide evidence that specific heterotrimeric G proteins regulate NRG-mediated signaling and gene transcription during rat muscle development.