Competitive binding of alpha-actinin and calmodulin to the NMDA receptor.
The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMDA (N-methyl-D-aspartate) receptors is mechanosensitive and dependent on the integrity of actin, suggesting a functionally important interaction between NMDA receptors and the postsynaptic cytoskeleton. alpha-Actinin-2, a member of the spectrin/dystrophin family ... of actin-binding proteins, is identified here as a brain postsynaptic density protein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95. alpha-Actinin-2 binds by its central rod domain to the cytoplasmic tail of both NR1 and NR2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-actinin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-actinin may play a role in both the localization of NMDA receptors and their modulation by Ca2+.
Mesh Terms:
Actins, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Brain, Calmodulin, Cells, Cultured, Hippocampus, Humans, Intracellular Signaling Peptides and Proteins, Kv1.4 Potassium Channel, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Potassium Channels, Potassium Channels, Voltage-Gated, Rats, Receptors, N-Methyl-D-Aspartate, Recombinant Fusion Proteins
Actins, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Brain, Calmodulin, Cells, Cultured, Hippocampus, Humans, Intracellular Signaling Peptides and Proteins, Kv1.4 Potassium Channel, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Potassium Channels, Potassium Channels, Voltage-Gated, Rats, Receptors, N-Methyl-D-Aspartate, Recombinant Fusion Proteins
Nature
Date: Jan. 30, 1997
PubMed ID: 9009191
View in: Pubmed Google Scholar
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