Reelin modulates NMDA receptor activity in cortical neurons

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Chen Y., Beffert U., Ertunc M., Tang T., Kavalali E., Bezprozvanny I., ...Daha Fazla

JOURNAL OF NEUROSCIENCE, cilt.25, sa.36, ss.8209-8216, 2005 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 36
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1523/jneurosci.1951-05.2005
  • Dergi Adı: JOURNAL OF NEUROSCIENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.8209-8216
  • Anahtar Kelimeler: neurotransmission, brain development, disabled, Apoer2, Vldlr, LTP, LONG-TERM POTENTIATION, D-ASPARTATE RECEPTOR, TYROSINE PHOSPHORYLATION, BRAIN-DEVELOPMENT, ALPHA-2-MACROGLOBULIN RECEPTOR, VLDL RECEPTOR, SRC FAMILY, DISABLED-1, MOUSE, KINASES
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.