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

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.

SUBMITTER: Yaka R

PROVIDER: S-EPMC122836 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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

Yaka Rami R Thornton Claire C Vagts Alicia J AJ Phamluong Khanhky K Bonci Antonello A Ron Dorit D

Proceedings of the National Academy of Sciences of the United States of America 20020409 8

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 slic ...[more]

PMID: 11943848

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