RESUMEN
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 beta1 (Gbeta1) 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 Gbeta1 and Gbeta2 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 Gbeta1 or Gbeta2 in COS7 cells attenuates NRG-induced extracellular signal-regulated kinase (ERK) 1/2 activation, whereas suppression of Gbeta2 expression in C2C12 myotubes enhances NRG-mediated ERK1/2 activation and c-fos transcription. These results suggest that expression of Gbeta 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.
