Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission

Rial Verde, E. M. , Lee-Osbourne, J., Worley, P. F., Malinow, R., Cline, H. T. (November 2006) Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron, 52 (3). pp. 461-74. ISSN 0896-6273 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17088212
DOI: 10.1016/j.neuron.2006.09.031

Abstract

Arc/Arg3.1 is an immediate-early gene whose expression levels are increased by strong synaptic activation, including synapse-strengthening activity patterns. Arc/Arg3.1 mRNA is transported to activated dendritic regions, conferring the distribution of Arc/Arg3.1 protein both temporal correlation with the inducing stimulus and spatial specificity. Here, we investigate the effect of increased Arc/Arg3.1 levels on synaptic transmission. Surprisingly, Arc/Arg3.1 reduces the amplitude of synaptic currents mediated by AMPA-type glutamate receptors (AMPARs). This effect is prevented by RNAi knockdown of Arc/Arg3.1, by deleting a region of Arc/Arg3.1 known to interact with endophilin 3 or by blocking clathrin-coated endocytosis of AMPARs. In the hippocampal slice, Arc/Arg3.1 results in removal of AMPARs composed of GluR2 and GluR3 subunits (GluR2/3). Finally, Arc/Arg3.1 expression occludes NMDAR-dependent long-term depression. Our results demonstrate that Arc/Arg3.1 reduces the number of GluR2/3 receptors leading to a decrease in AMPAR-mediated synaptic currents, consistent with a role in the homeostatic regulation of synaptic strength.

Item Type: Paper
Uncontrolled Keywords: Animals Animals Newborn Biotinylation methods Blotting Western methods Cytoskeletal Proteins genetics physiology Electric Stimulation methods Enzyme Inhibitors pharmacology Excitatory Amino Acid Agonists pharmacology Gene Expression physiology Green Fluorescent Proteins metabolism Hippocampus cytology Long-Term Depression (Physiology) drug effects physiology radiation effects Models, Biological Mutagenesis/physiology N-Methylaspartate pharmacology Nerve Tissue Proteins genetics physiology Neurons drug effects physiology radiation effects Okadaic Acid pharmacology Patch-Clamp Techniques methods RNA Interference physiology Rats Receptors AMPA physiology Statistics Nonparametric Synaptic Transmission physiology Time Factors alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid pharmacology
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics
CSHL Authors:
Communities: CSHL labs > Cline lab
CSHL labs > Malinow lab
Watson School > Publications
Depositing User: CSHL Librarian
Date: 9 November 2006
Date Deposited: 12 Dec 2011 16:22
Last Modified: 19 Sep 2014 18:50
PMCID: PMC3951199
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22885

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