Journal
NEURON
Volume 47, Issue 4, Pages 567-579Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2005.07.007
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Funding
- NHLBI NIH HHS [R37 HL063762, HL20948, HL63762] Funding Source: Medline
- NIMH NIH HHS [MH57014] Funding Source: Medline
- NINDS NIH HHS [NS43408] Funding Source: Medline
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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.
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