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

Rami Yaka; Claire Thornton; Alicia J. Vagts; Khanhky Phamluong; Antonello Bonci; Dorit Ron

doi:10.1073/pnas.062046299

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

Rami Yaka, Claire Thornton, Alicia J. Vagts, Khanhky Phamluong, Antonello Bonci, Dorit Ron^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

167 Scopus citations

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.

Original language	English
Pages (from-to)	5710-5715
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	99
Issue number	8
DOIs	https://doi.org/10.1073/pnas.062046299
State	Published - 16 Apr 2002
Externally published	Yes

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AU - Thornton, Claire

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AU - Phamluong, Khanhky

AU - Bonci, Antonello

AU - Ron, Dorit

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

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