Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Binding Sites / genetics
-
Carrier Proteins / metabolism*
-
Cells, Cultured
-
Cytoskeletal Proteins
-
Hippocampus / cytology
-
Hippocampus / metabolism
-
Intercellular Signaling Peptides and Proteins
-
Intracellular Signaling Peptides and Proteins
-
Mutagenesis, Site-Directed
-
Nerve Tissue Proteins / metabolism*
-
Neurons / cytology
-
Neurons / metabolism
-
Nuclear Proteins / metabolism
-
Protein Structure, Tertiary / genetics
-
Proto-Oncogene Proteins c-myc / genetics
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, AMPA / genetics
-
Receptors, AMPA / metabolism*
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Sindbis Virus / genetics
-
Synaptic Membranes / metabolism*
Substances
-
Adaptor Proteins, Signal Transducing
-
Carrier Proteins
-
Cytoskeletal Proteins
-
Grip1 protein, mouse
-
Grip1 protein, rat
-
Grip2 protein, rat
-
Intercellular Signaling Peptides and Proteins
-
Intracellular Signaling Peptides and Proteins
-
Nerve Tissue Proteins
-
Nuclear Proteins
-
PICK1 protein, rat
-
Proto-Oncogene Proteins c-myc
-
Receptors, AMPA
-
Recombinant Fusion Proteins
-
glutamate receptor ionotropic, AMPA 2