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

Céline Furne, Jerome Ricard, Jorge Ruben Cabrera, Laurent Pays, John R Bethea, Patrick Mehlen, Daniel J. Liebl

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1793
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Apoptosis
  • Dependence receptor
  • Eph receptor
  • Ephrin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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