論文 - 詳細
| RRC ID | 46197 |
|---|---|
| 著者 | Silva MC, Amaral MD, Morimoto RI. |
| タイトル | Neuronal reprograming of protein homeostasis by calcium-dependent regulation of the heat shock response. |
| ジャーナル | PLoS Genet |
| Abstract |
Protein quality control requires constant surveillance to prevent misfolding, aggregation, and loss of cellular function. There is increasing evidence in metazoans that communication between cells has an important role to ensure organismal health and to prevent stressed cells and tissues from compromising lifespan. Here, we show in C. elegans that a moderate increase in physiological cholinergic signaling at the neuromuscular junction (NMJ) induces the calcium (Ca(2+))-dependent activation of HSF-1 in post-synaptic muscle cells, resulting in suppression of protein misfolding. This protective effect on muscle cell protein homeostasis was identified in an unbiased genome-wide screening for modifiers of protein aggregation, and is triggered by downregulation of gei-11, a Myb-family factor and proposed regulator of the L-type acetylcholine receptor (AChR). This, in-turn, activates the voltage-gated Ca(2+) channel, EGL-19, and the sarcoplasmic reticulum ryanodine receptor in response to acetylcholine signaling. The release of calcium into the cytoplasm of muscle cells activates Ca(2+)-dependent kinases and induces HSF-1-dependent expression of cytoplasmic chaperones, which suppress misfolding of metastable proteins and stabilize the folding environment of muscle cells. This demonstrates that the heat shock response (HSR) can be activated in muscle cells by neuronal signaling across the NMJ to protect proteome health. |
| 巻・号 | 9(8) |
| ページ | e1003711 |
| 公開日 | 2013-8-1 |
| DOI | 10.1371/journal.pgen.1003711 |
| PII | PGENETICS-D-13-01182 |
| PMID | 24009518 |
| PMC | PMC3757039 |
| MeSH | Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Calmodulin / genetics Heat-Shock Response / genetics* Homeostasis / genetics* Humans Molecular Chaperones / metabolism Muscle Cells / metabolism Neuromuscular Junction / genetics* Neurons / metabolism Receptors, Cholinergic / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 5.175 |
| 引用数 | 12 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | 2 |
| 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 | tm6548 |