Plasma membrane insertion of the AMPA receptor GluA2 subunit is regulated by NSF binding and Q/R editing of the ion pore.
The delivery of AMPA receptors to the plasma membrane is a critical step both for the synaptic delivery of these receptors and for the regulation of synaptic transmission. To directly visualize fusion events of transport vesicles containing the AMPA receptor GluA2 subunit with the plasma membrane we used pHluorin-tagged GluA2 subunits and total internal reflection fluorescence microscopy. We demonstrate that the plasma membrane insertion of GluA2 requires the NSF binding site within its intracellular cytoplasmic domain and that RNA editing of the Q/R site in the ion channel region plays a key role in GluA2 plasma membrane insertion. Finally, we show that plasma membrane insertion of heteromeric GluA2/3 receptors follows the same rules as homomeric GluA2 receptors. These results demonstrate that the plasma membrane delivery of GluA2 containing AMPA receptors is regulated by its unique structural elements.
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yoichi
Y
Araki
Da-Ting
DT
Lin
Richard L
RL
Huganir
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D055503:Protein Multimerization; D021122:Protein Subunits; D017393:RNA Editing; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D021122:Protein Subunits; D018091:Receptors, AMPA; D011994:Recombinant Proteins; C104723:glutamate receptor ionotropic, AMPA 3; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat; C104722:glutamate receptor ionotropic, AMPA 2