title: Back signaling by the Nrg-1 intracellular domain.
abstract: Transmembrane isoforms of neuregulin-1 (Nrg-1), ligands for erbB receptors, include an extracellular domain with an EGF-like sequence and a highly conserved intracellular domain (ICD) of unknown function. In this paper, we demonstrate that transmembrane isoforms of Nrg-1 are bidirectional signaling molecules in neurons. The stimuli for Nrg-1 back signaling include binding of erbB receptor dimers to the extracellular domain of Nrg-1 and neuronal depolarization. These stimuli elicit proteolytic release and translocation of the ICD of Nrg-1 to the nucleus. Once in the nucleus, the Nrg-1 ICD represses expression of several regulators of apoptosis, resulting in decreased neuronal cell death in vitro. Thus, regulated proteolytic processing of Nrg-1 results in retrograde signaling that appears to mediate contact and activity-dependent survival of Nrg-1-expressing neurons.
authors.affiliation: Institute of Human Nutrition, 701 West 168th St., 5-503 New York, NY 10032, USA. dat1@columbia.edu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Bao
authors.forename: Deon
authors.initials: D
authors.lastname: Wolpowitz
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Role
authors.forename: David A
authors.initials: DA
authors.lastname: Talmage
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008854:Microscopy, Electron; D020890:Neuregulin-1 / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D010447:Peptide Hydrolases / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013136:Spiral Ganglion / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D020890:Neuregulin-1; D066246:ErbB Receptors; D010447:Peptide Hydrolases