論文 - 詳細
| RRC ID | 47314 |
|---|---|
| 著者 | Pavel M, Imarisio S, Menzies FM, Jimenez-Sanchez M, Siddiqi FH, Wu X, Renna M, O'Kane CJ, Crowther DC, Rubinsztein DC. |
| タイトル | CCT complex restricts neuropathogenic protein aggregation via autophagy. |
| ジャーナル | Nat Commun |
| Abstract |
Aberrant protein aggregation is controlled by various chaperones, including CCT (chaperonin containing TCP-1)/TCP-1/TRiC. Mutated CCT4/5 subunits cause sensory neuropathy and CCT5 expression is decreased in Alzheimer's disease. Here, we show that CCT integrity is essential for autophagosome degradation in cells or Drosophila and this phenomenon is orchestrated by the actin cytoskeleton. When autophagic flux is reduced by compromise of individual CCT subunits, various disease-relevant autophagy substrates accumulate and aggregate. The aggregation of proteins like mutant huntingtin, ATXN3 or p62 after CCT2/5/7 depletion is predominantly autophagy dependent, and does not further increase with CCT knockdown in autophagy-defective cells/organisms, implying surprisingly that the effect of loss-of-CCT activity on mutant ATXN3 or huntingtin oligomerization/aggregation is primarily a consequence of autophagy inhibition rather than loss of physiological anti-aggregation activity for these proteins. Thus, our findings reveal an essential partnership between two key components of the proteostasis network and implicate autophagy defects in diseases with compromised CCT complex activity. |
| 巻・号 | 7 |
| ページ | 13821 |
| 公開日 | 2016-12-8 |
| DOI | 10.1038/ncomms13821 |
| PII | ncomms13821 |
| PMID | 27929117 |
| PMC | PMC5155164 |
| MeSH | Animals Ataxin-3 / metabolism Autophagosomes / metabolism* Autophagy* Chaperonin Containing TCP-1 / metabolism* Drosophila Female HeLa Cells Humans Huntingtin Protein / metabolism* Lysosomes / metabolism Male Mice, Transgenic Protein Aggregation, Pathological / metabolism* RNA-Binding Proteins / metabolism |
| IF | 12.121 |
| 引用数 | 43 |
| WOS 分野 | 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 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 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 | 8439R-1 8439R-4 |