Schulz, T. W., Nakagawa, T., Licznerski, P., Pawlak, V., Kolleker, A., Rozov, A., Kim, J., Dittgen, T., Kohr, G., Sheng, M., Seeburg, P. H., Osten, P. (September 2004) Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. Journal of Neuroscience, 24 (39). pp. 8584-94. ISSN 0270-6474
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Abstract
The efficacy of excitatory transmission in the brain depends to a large extent on synaptic AMPA receptors, hence the importance of understanding the delivery and recycling of the receptors at the synaptic sites. Here we report a novel regulation of the AMPA receptor transport by a PDZ (postsynaptic density-95/Drosophila disc large tumor suppressor zona occludens 1) and LIM (Lin11/rat Isl-1/Mec3) domain-containing protein, RIL (reversion-induced LIM protein). We show that RIL binds to the AMPA glutamate receptor subunit GluR-A C-terminal peptide via its LIM domain and to alpha-actinin via its PDZ domain. RIL is enriched in the postsynaptic density fraction isolated from rat forebrain, strongly localizes to dendritic spines in cultured neurons, and coprecipitates, together with alpha-actinin, in a protein complex isolated by immunoprecipitation of AMPA receptors from forebrain synaptosomes. Functionally, in heterologous cells, RIL links AMPA receptors to the alpha-actinin/actin cytoskeleton, an effect that appears to apply selectively to the endosomal surface-internalized population of the receptors. In cultured neurons, an overexpression of recombinant RIL increases the accumulation of AMPA receptors in dendritic spines, both at the total level, as assessed by immunodetection of endogenous GluR-A-containing receptors, and at the synaptic surface, as assessed by recording of miniature EPSCs. Our results thus indicate that RIL directs the transport of GluR-A-containing AMPA receptors to and/or within dendritic spines, in an alpha-actinin/actin-dependent manner, and that such trafficking function promotes the synaptic accumulation of the receptors.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Actinin physiology Actins physiology Amino Acid Motifs Animals Cells Cultured DNA-Binding Proteins metabolism physiology Dendritic Spines metabolism Excitatory Postsynaptic Potentials physiology Hippocampus cytology metabolism Humans Neurons metabolism Protein Binding Protein Structure Tertiary Protein Transport Rats Rats Wistar Receptors AMPA metabolism Recombinant Fusion Proteins metabolism |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines |
| CSHL Authors: | |
| Communities: | CSHL labs > Osten lab |
| Depositing User: | CSHL Librarian |
| Date: | 29 September 2004 |
| Date Deposited: | 25 Jan 2012 21:54 |
| Last Modified: | 08 Apr 2013 15:21 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22474 |
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