論文 - 詳細
| RRC ID | 59609 |
|---|---|
| 著者 | Tang NH, Kim KW, Xu S, Blazie SM, Yee BA, Yeo GW, Jin Y, Chisholm AD. |
| タイトル | The mRNA Decay Factor CAR-1/LSM14 Regulates Axon Regeneration via Mitochondrial Calcium Dynamics. |
| ジャーナル | Curr Biol |
| Abstract |
mRNA decay factors regulate mRNA turnover by recruiting non-translating mRNAs and targeting them for translational repression and mRNA degradation. How mRNA decay pathways regulate cellular function in vivo with specificity is poorly understood. Here, we show that C. elegans mRNA decay factors, including the translational repressors CAR-1/LSM14 and CGH-1/DDX6, and the decapping enzymes DCAP-1/DCP1, function in neurons to differentially regulate axon development, maintenance, and regrowth following injury. In neuronal cell bodies, CAR-1 fully colocalizes with CGH-1 and partially colocalizes with DCAP-1, suggesting that mRNA decay components form at least two types of cytoplasmic granules. Following axon injury in adult neurons, loss of CAR-1 or CGH-1 results in increased axon regrowth and growth cone formation, whereas loss of DCAP-1 or DCAP-2 results in reduced regrowth. To determine how CAR-1 inhibits regrowth, we analyzed mRNAs bound to pan-neuronally expressed GFP::CAR-1 using a crosslinking and immunoprecipitation-based approach. Among the putative mRNA targets of CAR-1, we characterized the roles of micu-1, a regulator of the mitochondrial calcium uniporter MCU-1, in axon injury. We show that loss of car-1 results increased MICU-1 protein levels, and that enhanced axon regrowth in car-1 mutants is dependent on micu-1 and mcu-1. Moreover, axon injury induces transient calcium influx into axonal mitochondria, dependent on MCU-1. In car-1 loss-of-function mutants and in micu-1 overexpressing animals, the axonal mitochondrial calcium influx is more sustained, which likely underlies enhanced axon regrowth. Our data uncover a novel pathway that controls axon regrowth through axonal mitochondrial calcium uptake. |
| 巻・号 | 30(5) |
| ページ | 865-876.e7 |
| 公開日 | 2020-3-9 |
| DOI | 10.1016/j.cub.2019.12.061 |
| PII | S0960-9822(19)31694-X |
| PMID | 31983639 |
| PMC | PMC7147385 |
| MeSH | Animals Axons / physiology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Calcium / metabolism* Endoribonucleases / genetics* Endoribonucleases / metabolism Mitochondrial Dynamics Nerve Regeneration / genetics* RNA Nucleotidyltransferases / genetics* RNA Nucleotidyltransferases / metabolism RNA Stability RNA, Messenger / metabolism RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism |
| IF | 9.193 |
| 引用数 | 0 |
| 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 | 13 |
| 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 | tm1753 tm2470 |