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 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.
Greger
Ingo H
IH
Howard Hughes Medical Institute, Department of Biochemistry, NYU School of Medicine, New York 10016, USA.
Khatri
Latika
L
Ziff
Edward B
EB
D000581:Amidohydrolases / Q000494:pharmacology; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D000091342:Endoplasmic Reticulum Chaperone BiP; D005333:Fetus; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006360:Heat-Shock Proteins; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D012313:RNA / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics*; D021601:trans-Golgi Network / Q000378:metabolism / Q000648:ultrastructure
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D018091:Receptors, AMPA; D012313:RNA; D001120:Arginine; D006026:Glycoside Hydrolases; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase