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

Uwe Beffert, Edwin J. Weeber, Andre Durudas, Shenfeng Qiu, Irene Masiulis, J. David Sweatt, Wei Ping Li, Giselind Adelmann, Michael Frotscher, Robert E Hammer, Joachim Herz

Research output: Contribution to journalArticle

321 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)567-579
Number of pages13
JournalNeuron
Volume47
Issue number4
DOIs
StatePublished - Aug 18 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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    Beffert, U., Weeber, E. J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J. D., Li, W. P., Adelmann, G., Frotscher, M., Hammer, R. E., & Herz, J. (2005). Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron, 47(4), 567-579. https://doi.org/10.1016/j.neuron.2005.07.007