| 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
|
| リソース情報 |
| 線虫 |
tm395
tm598
tm3546 |
