論文 - 詳細
| RRC ID | 51380 |
|---|---|
| 著者 | Opperman KJ, Mulcahy B, Giles AC, Risley MG, Birnbaum RL, Tulgren ED, Dawson-Scully K, Zhen M, Grill B. |
| タイトル | The HECT Family Ubiquitin Ligase EEL-1 Regulates Neuronal Function and Development. |
| ジャーナル | Cell Rep |
| Abstract |
Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with intellectual disability, but it remains unknown whether HUWE1 functions in post-mitotic neurons to affect circuit function. Using genetics, pharmacology, and electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans, preferentially regulates GABAergic presynaptic transmission. Decreasing or increasing EEL-1 function alters GABAergic transmission and the excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to impaired locomotion and increased sensitivity to electroshock. Furthermore, multiple mutations associated with intellectual disability impair EEL-1 function. Although synaptic transmission defects did not result from abnormal synapse formation, sensitizing genetic backgrounds revealed that EEL-1 functions in the same pathway as the RING family ubiquitin ligase RPM-1 to regulate synapse formation and axon termination. These findings from a simple model circuit provide insight into the molecular mechanisms required to obtain E/I balance and could have implications for the link between HUWE1 and intellectual disability. |
| 巻・号 | 19(4) |
| ページ | 822-835 |
| 公開日 | 2017-4-25 |
| DOI | 10.1016/j.celrep.2017.04.003 |
| PII | S2211-1247(17)30462-X |
| PMID | 28445732 |
| PMC | PMC5475272 |
| MeSH | Aldicarb / toxicity Animals Animals, Genetically Modified / metabolism Axons / metabolism Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Electroshock GABAergic Neurons / metabolism* Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism Hypersensitivity / etiology Locomotion / drug effects Mutagenesis, Site-Directed Presynaptic Terminals / metabolism RNA Interference Signal Transduction Synapses / metabolism Synaptic Transmission / drug effects Ubiquitin-Protein Ligases / antagonists & inhibitors Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* |
| IF | 8.109 |
| 引用数 | 11 |
| 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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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 23 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1516 |