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NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1.

Rami Yaka·Claire Thornton·Alicia J Vagts·Khanhky Phamluong·Antonello Bonci·Dorit Ron
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Abstract

Phosphorylation regulates the function of ligand-gated ion channels such as the N-methyl d-aspartate (NMDA) receptor. Here we report a mechanism for modulation of the phosphorylation state and function of the NMDA receptor via an inhibitory scaffolding protein, RACK1. We found that RACK1 binds both the NR2B subunit of the NMDA receptor and the nonreceptor protein tyrosine kinase, Fyn. RACK1 inhibits Fyn phosphorylation of NR2B and decreases NMDA receptor-mediated currents in CA1 hippocampal slices. Peptides that disrupt the interactions between RACK1, NR2B, and Fyn induce phosphorylation and potentiate NMDA receptor-mediated currents. Therefore, RACK1 is a regulator of NMDA receptor function and may play a role in synaptic plasticity, addiction, learning, and memory.

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Amino Acid SequenceAnimalsDNA, ComplementaryDose-Response Relationship, DrugElectrophysiologyEscherichia coliGTP-Binding ProteinsGene Expression RegulationHippocampusHumansMaleMolecular Sequence DataNeoplasm ProteinsPeptidesPhosphorylationPrecipitin TestsProtein BindingProtein BiosynthesisProto-Oncogene ProteinsProto-Oncogene Proteins c-fynRatsRats, Sprague-DawleyReceptors for Activated C KinaseReceptors, Cell SurfaceReceptors, N-Methyl-D-AspartateRecombinant ProteinsTwo-Hybrid System TechniquesJournal ArticleResearch Support, Non-U.S. Gov't

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Rami Yaka, Claire Thornton, Alicia J Vagts, Khanhky Phamluong, Antonello Bonci, Dorit Ron. 2002-04-09. NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1.. https://doi.org/10.1073/pnas.062046299

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