| First Author | Bao J | Year | 2003 |
| Journal | J Cell Biol | Volume | 161 |
| Issue | 6 | Pages | 1133-41 |
| PubMed ID | 12821646 | Mgi Jnum | J:84095 |
| Mgi Id | MGI:2665205 | Doi | 10.1083/jcb.200212085 |
| Citation | Bao J, et al. (2003) Back signaling by the Nrg-1 intracellular domain. J Cell Biol 161(6):1133-41 |
| abstractText | 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. |
