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Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2.

Apolipoprotein E receptor 2 (Apoer2), a member of the LDL receptor gene family, and its ligand Reelin control neuronal migration during brain development. Apoer2 is also essential for induction of long-term potentiation (LTP) in the adult brain. Here we show that Apoer2 is present in the postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors. Reelin signaling through Apoer2 markedly enhances LTP through a mechanism that requires the presence of amino acids encoded by an exon in the intracellular domain of Apoer2. This exon is alternatively spliced in an activity-dependent manner and is required for Reelin-induced tyrosine phosphorylation of NMDA receptor subunits. Mice constitutively lacking the exon perform poorly in learning and memory tasks. Thus, alternative splicing of Apoer2, a novel component of the NMDA receptor complex, controls the modulation of NMDA receptor activity, synaptic neurotransmission, and memory by Reelin.

Pubmed ID: 16102539

Authors

  • Beffert U
  • Weeber EJ
  • Durudas A
  • Qiu S
  • Masiulis I
  • Sweatt JD
  • Li WP
  • Adelmann G
  • Frotscher M
  • Hammer RE
  • Herz J

Journal

Neuron

Publication Data

August 18, 2005

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL20948
  • Agency: NHLBI NIH HHS, Id: HL63762
  • Agency: NIMH NIH HHS, Id: MH57014
  • Agency: NINDS NIH HHS, Id: NS43408

Mesh Terms

  • Alternative Splicing
  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Cells, Cultured
  • Exons
  • Extracellular Matrix Proteins
  • Hippocampus
  • LDL-Receptor Related Proteins
  • Long-Term Potentiation
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Organ Culture Techniques
  • Phosphorylation
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Receptors, Lipoprotein
  • Receptors, N-Methyl-D-Aspartate
  • Serine Endopeptidases
  • Synapses
  • Synaptic Membranes
  • Synaptic Transmission