論文 - 詳細
| RRC ID | 21506 |
|---|---|
| 著者 | Chew YL, Fan X, Götz J, Nicholas HR. |
| タイトル | PTL-1 regulates neuronal integrity and lifespan in C. elegans. |
| ジャーナル | J Cell Sci |
| Abstract |
Protein with tau-like repeats (PTL-1) is the sole Caenorhabditis elegans homolog of tau and MAP2, which are members of the mammalian family of microtubule-associated proteins (MAPs). In mammalian neurons, tau and MAP2 are segregated, with tau being mainly localised to the axon and MAP2 mainly to the dendrite. In particular, tau plays a crucial role in pathology, as elevated levels lead to the formation of tau aggregates in many neurodegenerative conditions including Alzheimer's disease. We used PTL-1 in C. elegans to model the biological functions of a tau-like protein without the complication of functional redundancy that is observed among the mammalian MAPs. Our findings indicate that PTL-1 is important for the maintenance of neuronal health as animals age, as well as in the regulation of whole organism lifespan. In addition, gene dosage of PTL-1 is crucial because variations from wild-type levels are detrimental. We also observed that human tau is unable to robustly compensate for loss of PTL-1, although phenotypes observed in tau transgenic worms are dependent on the presence of endogenous PTL-1. Our data suggest that some of the effects of tau pathology result from the loss of physiological tau function and not solely from a toxic gain-of-function due to accumulation of tau. |
| 巻・号 | 126(Pt 9) |
| ページ | 2079-91 |
| 公開日 | 2013-5-1 |
| DOI | 10.1242/jcs.jcs124404 |
| PII | jcs.jcs124404 |
| PMID | 23525010 |
| PMC | PMC4068611 |
| MeSH | Alzheimer Disease / genetics Alzheimer Disease / metabolism Alzheimer Disease / pathology Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / metabolism Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Dosage Humans Longevity / physiology* Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Neurons / cytology Neurons / metabolism* tau Proteins / biosynthesis tau Proteins / genetics |
| IF | 4.573 |
| 引用数 | 32 |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | Caenorhabditis elegans ptl-1(tm543) |