Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2.
Journal:
Neuron 2005 AugAuthors:
Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J
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 amin
...[more]o 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.[less]
Mesh Headings:
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