RNA Editing at Arg607 Controls AMPA Receptor Exit from the Endoplasmic Reticulum

AMPA-receptor (AMPAR) transport to synapses plays a critical role in the modulation of synaptic strength. We show that the functionally critical GluR2 subunit stably resides in an intracellular pool in the endoplasmic reticulum (ER). GluR2 in this pool is extensively complexed with GluR3 but not wit...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2002-05, Vol.34 (5), p.759-772
Main Authors: Greger, Ingo H, Khatri, Latika, Ziff, Edward B
Format: Article
Language:English
Subjects:
Amidohydrolases - pharmacology
Amino Acid Motifs - genetics
Amino Acid Sequence - genetics
Animals
Arginine - genetics
Brain - metabolism
Brain - ultrastructure
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cells, Cultured
Cross-Linking Reagents - pharmacology
Editing
Endoplasmic Reticulum - metabolism
Endoplasmic Reticulum - ultrastructure
Fetus
Glycoside Hydrolases - pharmacology
Heat-Shock Proteins
Hippocampus - metabolism
Hippocampus - ultrastructure
Kinases
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Molecular Sequence Data
Molecular weight
Neurons - metabolism
Neurons - ultrastructure
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Protein Isoforms - drug effects
Protein Isoforms - genetics
Protein Isoforms - metabolism
Protein Transport - genetics
Proteins
Rats
Rats, Sprague-Dawley
Receptors, AMPA - genetics
Retention
RNA - genetics
RNA Editing - genetics
trans-Golgi Network - metabolism
trans-Golgi Network - ultrastructure
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Summary:AMPA-receptor (AMPAR) transport to synapses plays a critical role in the modulation of synaptic strength. We show that the functionally critical GluR2 subunit stably resides in an intracellular pool in the endoplasmic reticulum (ER). GluR2 in this pool is extensively complexed with GluR3 but not with GluR1, which is mainly confined to the cell surface. Mutagenesis revealed that elements in the C terminus including the PDZ motif are required for GluR2 forward-transport from the ER. Surprisingly, ER retention of GluR2 is controlled by Arg607 at the Q/R-editing site. Reversion to Gln (R607Q) resulted in rapid release from the pool and elevated surface expression of GluR2 in neurons. Therefore, Arg607 is a central regulator. In addition to channel gating, it also controls ER exit and may thereby ensure the availability of GluR2 for assembly into AMPARs.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(02)00693-1