A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux

Bryce Vissel, Johannes J. Krupp, Stephen F. Heinemann, Gary L. Westbrook

Research output: Contribution to journalArticle

197 Scopus citations

Abstract

Tyrosine phosphorylation can upregulate NMDA receptor activity during pathological and physiological alterations of synaptic strength. Here we describe downregulation of recombinant NR1/2A receptors by tyrosine dephosphorylation that requires agonist binding, but is independent of ion flux. The tyrosine residues involved in this new form of NMDA receptor modulation likely form a 'ring' adjacent to the last transmembrane domain. The downregulation was due to a reduction in the number of functional channels, and was blocked by co-expressing a dominant-negative μ2-subunit of the clathrin-adaptor protein AP-2. Our results provide a mechanism by which synaptic NMDA receptors can be modulated in a use-dependent manner even when the postsynaptic membrane is not sufficiently depolarized to relieve channel block by magnesium ions.

Original languageEnglish (US)
Pages (from-to)587-596
Number of pages10
JournalNature Neuroscience
Volume4
Issue number6
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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