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 RIS Download
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