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Here, we show that the deubiquitinating enzyme ubiquitin-specific protease-46 (USP-46) regulates the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of<jats:italic>Caenorhabditis elegans<\/jats:italic>. Mutants lacking<jats:italic>usp-46<\/jats:italic>have decreased GLR-1 in the ventral nerve cord and corresponding defects in GLR-1-dependent behaviors. The amount of ubiquitinated GLR-1 is increased in<jats:italic>usp-46<\/jats:italic>mutants. Mutations that block GLR-1 ubiquitination or receptor degradation in the multi-vesicular body\/lysosome prevent the decrease in GLR-1 observed in<jats:italic>usp-46<\/jats:italic>mutants. These data support a model in which USP-46 promotes GLR-1 abundance at synapses by deubiquitinating GLR-1 and preventing its degradation in the lysosome. This work suggests that the balance between the addition and removal of ubiquitin is important for glutamate receptor trafficking.<\/jats:p>","DOI":"10.1523\/jneurosci.4765-10.2011","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T18:19:30Z","timestamp":1296152370000},"page":"1341-1354","source":"Crossref","is-referenced-by-count":56,"title":["The Deubiquitinating Enzyme USP-46 Negatively Regulates the Degradation of Glutamate Receptors to Control Their Abundance in the Ventral Nerve Cord of<i>Caenorhabditis elegans<\/i>"],"prefix":"10.1523","volume":"31","author":[{"given":"Jennifer R.","family":"Kowalski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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