論文 - 詳細
| RRC ID | 3383 |
|---|---|
| 著者 | Gottschalk A, Almedom RB, Schedletzky T, Anderson SD, Yates JR 3rd, Schafer WR. |
| タイトル | Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans. |
| ジャーナル | EMBO J |
| Abstract |
Nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory neurotransmission in neurons and muscles. To identify nAChR accessory proteins, which may regulate their expression or function, we performed tandem affinity purification of the levamisole-sensitive nAChR from Caenorhabditis elegans, mass spectrometry of associated components, and RNAi-based screening for effects on in vivo nicotine sensitivity. Among the proteins identified was the calcineurin A subunit TAX-6, which appeared to function as a negative regulator of nAChR activity. We also identified five proteins not previously linked to nAChR function, whose inactivation conferred nicotine resistance, implicating them as positive regulators of nAChR activity. Of these, the copine NRA-1 colocalized with the levamisole receptor at neuronal and muscle plasma membranes, and, when mutated, caused reduced synaptic nAChR expression. Loss of SOC-1, which acts in receptor tyrosine kinase (RTK) signaling, also reduced synaptic levamisole receptor levels, as did mutations in the fibroblast growth factor receptor EGL-15, and another RTK, CAM-1. Thus, tandem affinity purification is a viable approach to identify novel proteins regulating neurotransmitter receptor activity or expression in model systems like C. elegans. |
| 巻・号 | 24(14) |
| ページ | 2566-78 |
| 公開日 | 2005-7-20 |
| DOI | 10.1038/sj.emboj.7600741 |
| PII | 7600741 |
| PMID | 15990870 |
| PMC | PMC1176467 |
| MeSH | Affinity Labels Animals Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Genes, Reporter Levamisole / metabolism* Muscles / drug effects Neurons / drug effects Nicotine / pharmacology Nicotinic Agonists / pharmacology RNA Interference Receptors, Cholinergic / chemistry Receptors, Cholinergic / metabolism Receptors, Fibroblast Growth Factor / metabolism Receptors, Nicotinic / chemistry Receptors, Nicotinic / metabolism* Synapses / metabolism Time Factors |
| IF | 9.889 |
| 引用数 | 100 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | tm1395 tm1453 tm1649 |