論文 - 詳細
| RRC ID | 54544 |
|---|---|
| 著者 | Kukharsky MS, Quintiero A, Matsumoto T, Matsukawa K, An H, Hashimoto T, Iwatsubo T, Buchman VL, Shelkovnikova TA. |
| タイトル | Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis. |
| ジャーナル | Mol Neurodegener |
| Abstract |
BACKGROUND:Mutations in calcium-responsive transactivator (CREST) encoding gene have been recently linked to ALS. Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles. RESULTS:We demonstrate that CREST is prone to aggregation and co-aggregates with FUS but not with other two ALS-linked proteins, TDP-43 and TAF15, in cultured cells. Aggregation of CREST affects paraspeckle integrity, probably by trapping other paraspeckle proteins within aggregates. Like several other ALS-associated proteins, CREST is recruited to induced stress granules. Neither of the CREST mutations described in ALS alters its subcellular localization, stress granule recruitment or detergent solubility; however Q388stop mutation results in elevated steady-state levels and more frequent nuclear aggregation of the protein. Both wild-type protein and its mutants negatively affect neurite network complexity of unstimulated cultured neurons when overexpressed, with Q388stop mutation being the most deleterious. When overexpressed in the fly eye, wild-type CREST or its mutants lead to severe retinal degeneration without obvious differences between the variants. CONCLUSIONS:Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis. |
| 巻・号 | 10 |
| ページ | 20 |
| 公開日 | 2015-4-10 |
| DOI | 10.1186/s13024-015-0014-y |
| PII | 10.1186/s13024-015-0014-y |
| PMID | 25888396 |
| PMC | PMC4428507 |
| MeSH | Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism* Animals Calcium / metabolism* Cell Line Cells, Cultured DNA-Binding Proteins / metabolism Humans Mice Mutation / genetics Neurons / metabolism* RNA-Binding Protein FUS / genetics RNA-Binding Protein FUS / metabolism Trans-Activators / metabolism* |
| IF | 8.274 |
| 引用数 | 11 |
| リソース情報 | |
| ショウジョウバエ | |