@article{1c420b09751f4c3d84a6e59fe4ffab5a,
title = "Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2",
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.",
author = "Uwe Beffert and Weeber, {Edwin J.} and Andre Durudas and Shenfeng Qiu and Irene Masiulis and Sweatt, {J. David} and Li, {Wei Ping} and Giselind Adelmann and Michael Frotscher and Hammer, {Robert E} and Joachim Herz",
note = "Funding Information: This paper is dedicated to the memory of Melanie Reuben (1969–2002). We thank Johannes Nimpf for Apoer2 antibodies; Thomas S{\"u}dhof for synaptophysin antibodies and the PSD-95 plasmid; Peter Seeburg for NR2A plasmid; Jeremiah Shepard for RNA samples; and Mike Brown, Joe Goldstein, Steve McKnight, Thomas S{\"u}dhof, and Klaus Giehl for critical reading of the manuscript. We are indebted to Wen-Ling Niu, Huichuan Reyna, Iza Lesznicki, Jenny Garcia, Megan Davenport, Karen Brown, Debbie Morgan, Jeff Stark, John Shelton, and Elizabeth Lummus for excellent technical assistance and to Michael Gotthardt, Craig Powell, and Gilbert Gallardo for advice and help. Supported by National Institutes of Health (NIH) grants HL20948, HL63762, and NS43408; the Alzheimer{\textquoteright}s Association; the Wolfgang-Paul Award of the Humboldt Foundation; and the Perot Family Foundation (to J.H.) and by NIH grant MH57014 and a grant from the American Health Assistance Foundation (to J.D.S.). U.B. received fellowships from the Human Frontier Science Program and from the Canadian Institutes of Health Research. M.F. is supported by SFB505 from the Deutsche Forschungsgemeinschaft. ",
year = "2005",
month = aug,
day = "18",
doi = "10.1016/j.neuron.2005.07.007",
language = "English (US)",
volume = "47",
pages = "567--579",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}