title: Expression of G protein beta subunits in rat skeletal muscle after nerve injury: Implication in the regulation of neuregulin signaling.
abstract: 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.
authors: Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
authors: K-C
authors: KC
authors: Lok
authors: A K Y
authors: AK
authors: Fu
authors: F C F
authors: FC
authors: Ip
authors: Y H
authors: YH
authors: Wong
authors: N Y
authors: NY
authors: Ip
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian; D044387:GTP-Binding Protein beta Subunits; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000166:cytology*; D020880:Neuregulins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D020426:Sciatic Neuropathy / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D000779:Anesthetics, Local; D044387:GTP-Binding Protein beta Subunits; D020880:Neuregulins; D013779:Tetrodotoxin