論文 - 詳細
| RRC ID | 32444 |
|---|---|
| 著者 | Azuma Y, Tokuda T, Shimamura M, Kyotani A, Sasayama H, Yoshida T, Mizuta I, Mizuno T, Nakagawa M, Fujikake N, Ueyama M, Nagai Y, Yamaguchi M. |
| タイトル | Identification of ter94, Drosophila VCP, as a strong modulator of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS. |
| ジャーナル | Hum Mol Genet |
| Abstract |
In humans, mutations in the fused in sarcoma (FUS) gene have been identified in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). Cabeza (Caz) is the Drosophila ortholog of human FUS. Previously, we established Drosophila models of ALS harboring Caz-knockdown. These flies develop locomotive deficits and anatomical defects in motoneurons (MNs) at neuromuscular junctions; these phenotypes indicate that loss of physiological FUS functions in the nucleus can cause MN degeneration similar to that seen in FUS-related ALS. Here, we aimed to explore molecules that affect these ALS-like phenotypes of our Drosophila models with eye-specific and neuron-specific Caz-knockdown. We examined several previously reported ALS-related genes and found genetic links between Caz and ter94, the Drosophila ortholog of human Valosin-containing protein (VCP). Genetic crossing the strongest loss-of-function allele of ter94 with Caz-knockdown strongly enhanced the rough-eye phenotype and the MN-degeneration phenotype caused by Caz-knockdown. Conversely, the overexpression of wild-type ter94 in the background of Caz-knockdown remarkably suppressed those phenotypes. Our data demonstrated that expression levels of Drosophila VCP ortholog dramatically modified the phenotypes caused by Caz-knockdown in either direction, exacerbation or remission. Our results indicate that therapeutic agents that up-regulate the function of human VCP could modify the pathogenic processes that lead to the degeneration of MNs in ALS. |
| 巻・号 | 23(13) |
| ページ | 3467-80 |
| 公開日 | 2014-7-1 |
| DOI | 10.1093/hmg/ddu055 |
| PII | ddu055 |
| PMID | 24497576 |
| MeSH | Animals Animals, Genetically Modified Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Central Nervous System / cytology Central Nervous System / metabolism Compound Eye, Arthropod / metabolism Compound Eye, Arthropod / pathology Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Motor Neurons / metabolism* Mutation RNA-Binding Protein FUS / genetics RNA-Binding Protein FUS / metabolism* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Transcription Factor TFIID / genetics Transcription Factor TFIID / metabolism* Valosin Containing Protein |
| IF | 5.101 |
| 引用数 | 25 |
| WOS 分野 | GENETICS & HEREDITY 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 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 | |
| ショウジョウバエ | DGRC#107870 DGRC#106718 |