PT  - JOURNAL ARTICLE
AU  - Ying Chen
AU  - Uwe Beffert
AU  - Mert Ertunc
AU  - Tie-Shan Tang
AU  - Ege T. Kavalali
AU  - Ilya Bezprozvanny
AU  - Joachim Herz
TI  - Reelin Modulates NMDA Receptor Activity in Cortical Neurons
AID  - 10.1523/JNEUROSCI.1951-05.2005
DP  - 2005 Sep 07
TA  - The Journal of Neuroscience
PG  - 8209--8216
VI  - 25
IP  - 36
4099  - http://www.jneurosci.org/content/25/36/8209.short
4100  - http://www.jneurosci.org/content/25/36/8209.full
SO  - J. Neurosci.2005 Sep 07; 25
AB  - 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.