論文 - 詳細
| RRC ID | 11545 |
|---|---|
| 著者 | Kanuka H, Hiratou T, Igaki T, Kanda H, Kuranaga E, Sawamoto K, Aigaki T, Okano H, Miura M. |
| タイトル | Gain-of-function screen identifies a role of the Sec61alpha translocon in Drosophila postmitotic neurotoxicity. |
| ジャーナル | Biochim Biophys Acta |
| Abstract |
To elucidate the intrinsic mechanisms of neurotoxicity induction, including those underlying neural cell death and neurodegeneration, we developed a gain-of-function screen for gene products causing neural cell loss. To identify novel genes with a cell-death-related function in neurons, we screened 4,964 Drosophila GS lines, in which one or two genes from much of the Drosophila genome can be overexpressed. Approximately 0.68% of the GS lines produced phenotypes involving a loss of postmitotic neurons. Of these, we identified and characterized the endd2 gene, which encodes the Drosophila ortholog of Sec61alpha (DSec61alpha), an endoplasmic reticulum protein with protein translocation activity. Ectopic expression of DSec61alpha caused neural cell death accompanied by the accumulation of ubiquitinated proteins, which was mediated by DSec61alpha's translocon activity. This supported our previous observation that the DSec61alpha translocon contributes to expanded polyglutamine-mediated neuronal toxicity, which is also associated with ubiquitinated protein accumulation. These data suggest that the translocon may be a novel component of neural cell death and degeneration pathways. Our approach can be used to identify potential neurotoxic factors within the whole genome, which will increase our understanding of the molecular mechanisms of various types of cell death, including those associated with human neurodegenerative diseases. |
| 巻・号 | 1726(3) |
| ページ | 225-37 |
| 公開日 | 2005-11-30 |
| DOI | 10.1016/j.bbagen.2005.06.020 |
| PII | S0304-4165(05)00183-2 |
| PMID | 16243437 |
| MeSH | Animals Cell Death* Cell Line Drosophila / cytology Drosophila / genetics* Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / physiology* Endoplasmic Reticulum / metabolism Eye / cytology Genetic Complementation Test Membrane Proteins / genetics Membrane Proteins / physiology* Membrane Transport Proteins Mitosis Models, Biological Mutagenesis Neurons / cytology* Photoreceptor Cells, Invertebrate / cytology Protein Transport SEC Translocation Channels Saccharomyces cerevisiae Proteins / genetics |
| IF | 3.411 |
| 引用数 | 12 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR 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 | |
| ショウジョウバエ | DGRC#119556 |