EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis

Eph receptors have been implicated in regulating a diverse array of cellular functions in the developing nervous system. Recently, Eph receptors have been shown to promote cell death in adult germinal zones; however, their mechanisms of action remain ill-defined. In this study, we demonstrate that E...

Full description

Saved in:
Bibliographic Details
Published in:Biochimica et biophysica acta 2009-02, Vol.1793 (2), p.231-238
Main Authors: Furne, Céline, Ricard, Jerome, Cabrera, Jorge Ruben, Pays, Laurent, Bethea, John R., Mehlen, Patrick, Liebl, Daniel J.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Caspase 3 - metabolism
Cell Line
Cerebral Ventricles - drug effects
Cerebral Ventricles - enzymology
Cerebral Ventricles - pathology
Dependence receptor
Enzyme Activation - drug effects
Eph receptor
Ephrin
Ephrin-B3 - pharmacology
Humans
Ligands
Male
Mice
Neurogenesis - drug effects
Phosphorylation - drug effects
Receptor, EphA4 - metabolism
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - enzymology
Substrate Specificity - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Eph receptors have been implicated in regulating a diverse array of cellular functions in the developing nervous system. Recently, Eph receptors have been shown to promote cell death in adult germinal zones; however, their mechanisms of action remain ill-defined. In this study, we demonstrate that EphA4 is a new member of the dependence receptors family, which can initiate cell death in the absence of its ligand ephrinB3. Upon removal of its ligand, EphA4 triggers cell death that is dependent on caspase activation as caspase inhibitors prevent cell death. EphA4 itself is cleaved by caspase-3-like caspase in the intracellular domain at position D773/774, which is necessary for cell death initiation as mutation of the cleavage site abolishes apoptosis. In the adult subventricular zone, abolishing ephrinB3 results in increased cell death, while the absence of EphA4 results in excessive numbers of neuroblasts. Furthermore, infusion of soluble ephrinB3 into the lateral ventricle reduced cell death, and together these results support a dependence role for EphA4 in adult neurogenesis.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2008.09.009