Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor

Osten, P., Khatri, L., Perez, J. L., Köhr, G., Giese, G., Daly, C., Schulz, T. W., Wensky, A., Lee, L. M., Ziff, E. B. (2000) Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor. Neuron, 27 (2). pp. 313-325. ISSN 08966273 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/10985351
DOI: 10.1016/S0896-6273(00)00039-8

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 MycGluR2Δ1-10, which lacks the PDZ binding site, the overall dendritic intracellular transport and the synaptic surface targeting were not affected. However, over time, Myc-GluR2Δ1-10 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.

Item Type: Paper
Uncontrolled Keywords: AMPA receptor article binding site endocytosis hippocampus human human cell intracellular transport mutagenesis priority journal synapse vesicle synaptic transmission Adaptor Proteins, Signal Transducing Animals Binding Sites Carrier Proteins Cells, Cultured Mutagenesis, Site-Directed Nerve Tissue Proteins Neurons Nuclear Proteins Protein Structure, Tertiary Proto-Oncogene Proteins c-myc Rats Rats, Sprague-Dawley Receptors, AMPA Recombinant Fusion Proteins Sindbis Virus Synaptic Membranes
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: Matt Covey
Date Deposited: 05 Apr 2013 01:39
Last Modified: 05 Apr 2013 01:39
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28097

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