Abstract
Regulated delivery and removal of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) from postsynaptic elements has been proposed as a mechanism for regulating synaptic strength. Here we test the role of ubiquitin in regulating synapses that contain a C. elegans GluR, GLR-1. GLR-1 receptors were ubiquitinated in vivo. Mutations that decreased ubiquitination of GLR-1 increased the abundance of GLR-1 at synapses and altered locomotion behavior in a manner that is consistent with increased synaptic strength. By contrast, overexpression of ubiquitin decreased the abundance of GLR-1 at synapses and decreased the density of GLR-1-containing synapses, and these effects were prevented by mutations in the unc-11 gene, which encodes a clathrin adaptin protein (AP180). These results suggest that ubiquitination of GLR-1 receptors regulates synaptic strength and the formation or stability of GLR-1-containing synapses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Vesicular Transport
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Animals
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Caenorhabditis elegans / cytology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cytoplasmic Granules / genetics
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Cytoplasmic Granules / metabolism
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Gene Expression Regulation / genetics
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Green Fluorescent Proteins
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Indicators and Reagents / metabolism
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Luminescent Proteins / metabolism
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Macromolecular Substances
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Transport Proteins*
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Monomeric Clathrin Assembly Proteins*
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Motor Activity / genetics
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nervous System / cytology
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Nervous System / metabolism*
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Neuronal Plasticity / physiology*
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R-SNARE Proteins
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Receptors, AMPA
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Receptors, Glutamate / genetics
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Receptors, Glutamate / metabolism*
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Synaptic Membranes / metabolism*
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Synaptic Membranes / ultrastructure
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Synaptic Transmission / genetics
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Ubiquitin / genetics
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Ubiquitin / metabolism*
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Vesicular Glutamate Transport Protein 1
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Vesicular Transport Proteins*
Substances
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Adaptor Proteins, Vesicular Transport
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Indicators and Reagents
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Luminescent Proteins
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Macromolecular Substances
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Membrane Proteins
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Membrane Transport Proteins
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Monomeric Clathrin Assembly Proteins
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Nerve Tissue Proteins
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R-SNARE Proteins
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Receptors, AMPA
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Receptors, Glutamate
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Ubiquitin
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Vesicular Glutamate Transport Protein 1
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Vesicular Transport Proteins
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clathrin assembly protein AP180
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glr-1 protein, C elegans
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unc-11 protein, C elegans
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Green Fluorescent Proteins