Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans.
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.
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Michelle
M
Burbea
Lars
L
Dreier
Jeremy S
JS
Dittman
Maria E
ME
Grunwald
Joshua M
JM
Kaplan
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D034041:Monomeric Clathrin Assembly Proteins; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D050683:R-SNARE Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D025801:Ubiquitin; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins; C439023:clathrin assembly protein AP180; C096470:glr-1 protein, C elegans; C120753:unc-11 protein, C elegans; D049452:Green Fluorescent Proteins