Reelin modulates NMDA receptor activity in cortical neurons

Ying Chen, Uwe Beffert, Mert Ertunc, Tie Shan Tang, Ege T. Kavalali, Ilya Bezprozvanny, Joachim Herz

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Reelin, a large protein that regulates neuronal migration during embryonic development, activates a conserved signaling pathway that requires its receptors, very low-density lipoprotein receptor and apolipoprotein E receptor 2, the cytoplasmic adaptor protein Disabled-1 (Dab1), and Src family kinases (SFK). Reelin also markedly enhances long-term potentiation in the adult hippocampus, suggesting that this developmental signaling pathway can physiologically modulate learning and behavior. Here, we show that Reelin can regulate NMDA-type glutamate receptor activity through a mechanism that requires SFKs and Dab1. Reelin mediates tyrosine phosphorylation of and potentiates calcium influx through NMDA receptors in primary wild-type cortical neurons but not in Dab1 knock-out neurons or in cells in which Reelin binding to its receptors is blocked by a receptor antagonist. Inhibition of SFK abolishes Reelin-induced and glutamate-dependent enhancement of calcium influx. We also show that Reelin-induced augmentation of Ca2+ entry through NMDA receptors increases phosphorylation and nuclear translocation of the transcription factor cAMP-response element binding protein. Thus, Reelin may physiologically modulate learning and memory by modulating NMDA receptor functions.

Original languageEnglish (US)
Pages (from-to)8209-8216
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number36
DOIs
StatePublished - Sep 7 2005

Keywords

  • Apoer2
  • Brain development
  • Disabled
  • LTP
  • Neurotransmission
  • Vldlr

ASJC Scopus subject areas

  • Neuroscience(all)

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