title: Regulation of neuregulin/ErbB signaling by contractile activity in skeletal muscle.
abstract: Putative roles of neuregulin (NRG) and the ErbB receptors in skeletal muscle biology include myogenesis, ACh receptor expression, and glucose transport. To date, however, the physiological regulation of NRG/ErbB signaling has not been examined. We tested the hypothesis that contractile activity in vivo induces NRG/ErbB activation. Rat hindlimb muscle contraction was elicited with a single bout of electrical stimulation (RX) or treadmill running (EX). Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB2, ErbB3, and ErbB4 receptors in adult skeletal muscle. Both RX and EX significantly increased phosphorylation of all NRG receptors. Furthermore, contraction induced a shift in the expression profile of NRG, consistent with proteolytic processing of a transmembrane isoform. Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB2, ErbB3, and ErbB4 signaling in vivo. To our knowledge, this is the first demonstration of physiological regulation of NRG/ErbB signaling in any organ and implicates this pathway in the metabolic and proliferative responses of skeletal muscle to exercise.
authors.affiliation: Myocardial Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston 02218, USA.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Lebrasseur
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Coté
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Miller
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D066246:ErbB Receptors / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D020880:Neuregulins / Q000502:physiology*; D018739:Oncogene Proteins v-erbB / Q000502:physiology*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D020893:Receptor, ErbB-3 / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D066246:ErbB Receptors; D020880:Neuregulins; D018739:Oncogene Proteins v-erbB; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587691:Erbb4 protein, rat