Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor.
We studied the role of PDZ proteins GRIP, ABP, and PICK1 in GluR2 AMPA receptor trafficking. An epitope-tagged MycGluR2 subunit, when expressed in hippocampal cultured neurons, was specifically targeted to the synaptic surface. With the mutant MycGluR2delta1-10, which lacks the PDZ binding site, the overall dendritic intracellular transport and the synaptic surface targeting were not affected. However, over time, Myc-GluR2delta1-10 accumulated at synapses significantly less than MycGluR2. Notably, a single residue substitution, S880A, which blocks binding to ABP/GRIP but not to PICK1, reduced synaptic accumulation to the same extent as the PDZ site truncation. We conclude that the association of GluR2 with ABP and/or GRIP but not PICK1 is essential for maintaining the synaptic surface accumulation of the receptor, possibly by limiting its endocytotic rate.
Osten
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Max-Planck Institute for Medical Research, Department of Molecular Neurobiology, Heidelberg, Germany. posten@mpimf-heidelberg.mpg.de
Khatri
L
L
Perez
J L
JL
Köhr
G
G
Giese
G
G
Daly
C
C
Schulz
T W
TW
Wensky
A
A
Lee
L M
LM
Ziff
E B
EB
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012845:Sindbis Virus / Q000235:genetics; D013570:Synaptic Membranes / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; C118486:Grip2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D016271:Proto-Oncogene Proteins c-myc; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C104722:glutamate receptor ionotropic, AMPA 2