論文 - 詳細
| RRC ID | 46627 |
|---|---|
| 著者 | Kramer LB, Shim J, Previtera ML, Isack NR, Lee MC, Firestein BL, Rongo C. |
| タイトル | UEV-1 is an ubiquitin-conjugating enzyme variant that regulates glutamate receptor trafficking in C. elegans neurons. |
| ジャーナル | PLoS One |
| Abstract |
The regulation of AMPA-type glutamate receptor (AMPAR) membrane trafficking is a key mechanism by which neurons regulate synaptic strength and plasticity. AMPAR trafficking is modulated through a combination of receptor phosphorylation, ubiquitination, endocytosis, and recycling, yet the factors that mediate these processes are just beginning to be uncovered. Here we identify the ubiquitin-conjugating enzyme variant UEV-1 as a regulator of AMPAR trafficking in vivo. We identified mutations in uev-1 in a genetic screen for mutants with altered trafficking of the AMPAR subunit GLR-1 in C. elegans interneurons. Loss of uev-1 activity results in the accumulation of GLR-1 in elongated accretions in neuron cell bodies and along the ventral cord neurites. Mutants also have a corresponding behavioral defect--a decrease in spontaneous reversals in locomotion--consistent with diminished GLR-1 function. The localization of other synaptic proteins in uev-1-mutant interneurons appears normal, indicating that the GLR-1 trafficking defects are not due to gross deficiencies in synapse formation or overall protein trafficking. We provide evidence that GLR-1 accumulates at RAB-10-containing endosomes in uev-1 mutants, and that receptors arrive at these endosomes independent of clathrin-mediated endocytosis. UEV-1 homologs in other species bind to the ubiquitin-conjugating enzyme Ubc13 to create K63-linked polyubiquitin chains on substrate proteins. We find that whereas UEV-1 can interact with C. elegans UBC-13, global levels of K63-linked ubiquitination throughout nematodes appear to be unaffected in uev-1 mutants, even though UEV-1 is broadly expressed in most tissues. Nevertheless, ubc-13 mutants are similar in phenotype to uev-1 mutants, suggesting that the two proteins do work together to regulate GLR-1 trafficking. Our results suggest that UEV-1 could regulate a small subset of K63-linked ubiquitination events in nematodes, at least one of which is critical in regulating GLR-1 trafficking. |
| 巻・号 | 5(12) |
| ページ | e14291 |
| 公開日 | 2010-12-13 |
| DOI | 10.1371/journal.pone.0014291 |
| PMID | 21179194 |
| PMC | PMC3001443 |
| MeSH | Animals Behavior, Animal Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Clathrin / chemistry Endocytosis Gene Expression Regulation* Genetic Variation Interneurons / metabolism Models, Biological Models, Genetic Mutation Receptors, AMPA / metabolism Receptors, Glutamate / metabolism* Ubiquitin / metabolism* Ubiquitin-Conjugating Enzymes / genetics Ubiquitin-Conjugating Enzymes / physiology* |
| IF | 2.74 |
| 引用数 | 18 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 線虫 | tm395 tm598 tm3546 |