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 language | English (US) |
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Pages (from-to) | 587-596 |
Number of pages | 10 |
Journal | Nature Neuroscience |
Volume | 4 |
Issue number | 6 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
ASJC Scopus subject areas
- General Neuroscience