Back signaling by the Nrg-1 intracellular domain.
J Cell Biol
; 161(6): 1133-41, 2003 Jun 23.
Article
in En
| MEDLINE
| ID: mdl-12821646
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Cell Membrane
/
Cell Survival
/
Neuregulin-1
/
Neurons, Afferent
Limits:
Animals
Language:
En
Journal:
J Cell Biol
Year:
2003
Type:
Article
Affiliation country:
United States