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

192 Citations (Scopus)

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

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N-Methyl-D-Aspartate Receptors
Neurons
src-Family Kinases
Phosphorylation
Learning
Calcium
Cyclic AMP Response Element-Binding Protein
Long-Term Potentiation
Glutamate Receptors
Embryonic Development
Tyrosine
Glutamic Acid
Hippocampus
Proteins
Transcription Factors

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reelin modulates NMDA receptor activity in cortical neurons. / Chen, Ying; Beffert, Uwe; Ertunc, Mert; Tang, Tie Shan; Kavalali, Ege T.; Bezprozvanny, Ilya; Herz, Joachim.

In: Journal of Neuroscience, Vol. 25, No. 36, 07.09.2005, p. 8209-8216.

Research output: Contribution to journalArticle

Chen, Ying ; Beffert, Uwe ; Ertunc, Mert ; Tang, Tie Shan ; Kavalali, Ege T. ; Bezprozvanny, Ilya ; Herz, Joachim. / Reelin modulates NMDA receptor activity in cortical neurons. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 36. pp. 8209-8216.
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