Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL

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...

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Bibliographic Details
Published in:The Journal of neuroscience 2004-09, Vol.24 (39), p.8584-8594
Main Authors: Schulz, Torsten W, Nakagawa, Terunaga, Licznerski, Pawel, Pawlak, Verena, Kolleker, Alexander, Rozov, Andrei, Kim, Jinhyun, Dittgen, Tanjew, Köhr, Georg, Sheng, Morgan, Seeburg, Peter H, Osten, Pavel
Format: Article
Language:English
Subjects:
Actinin - physiology
Actins - physiology
Amino Acid Motifs
Animals
Cells, Cultured
Cellular/Molecular
Dendritic Spines - metabolism
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Excitatory Postsynaptic Potentials - physiology
Hippocampus - cytology
Hippocampus - metabolism
Humans
LIM Domain Proteins
Neurons - metabolism
Protein Binding
Protein Structure, Tertiary
Protein Transport
Rats
Rats, Wistar
Receptors, AMPA - metabolism
Recombinant Fusion Proteins - metabolism
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2100-04.2004