論文 - 詳細
| RRC ID | 59379 |
|---|---|
| 著者 | McGough IJ, de Groot REA, Jellett AP, Betist MC, Varandas KC, Danson CM, Heesom KJ, Korswagen HC, Cullen PJ. |
| タイトル | SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion. |
| ジャーナル | Nat Commun |
| Abstract |
Wntless transports Wnt morphogens to the cell surface and is required for Wnt secretion and morphogenic gradients formation. Recycling of endocytosed Wntless requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi transport pathway. Here we demonstrate the essential role of SNX3-retromer assembly for Wntless transport and report that SNX3 associates with an evolutionary conserved endosome-associated membrane re-modelling complex composed of MON2, DOPEY2 and the putative aminophospholipid translocase, ATP9A. In vivo suppression of Ce-mon-2, Ce-pad-1 or Ce-tat-5 (respective MON2, DOPEY2 and ATP9A orthologues) phenocopy a loss of SNX3-retromer function, leading to enhanced lysosomal degradation of Wntless and a Wnt phenotype. Perturbed Wnt signalling is also observed upon overexpression of an ATPase-inhibited TAT-5(E246Q) mutant, suggesting a role for phospholipid flippase activity during SNX3-retromer-mediated Wntless sorting. Together, these findings provide in vitro and in vivo mechanistic details to describe SNX3-retromer-mediated transport during Wnt secretion and the formation of Wnt-morphogenic gradients. |
| 巻・号 | 9(1) |
| ページ | 3737 |
| 公開日 | 2018-9-13 |
| DOI | 10.1038/s41467-018-06114-3 |
| PII | 10.1038/s41467-018-06114-3 |
| PMID | 30213940 |
| PMC | PMC6137200 |
| MeSH | Adenosine Triphosphatases / metabolism* Animals Biological Transport Caenorhabditis elegans Endosomes / metabolism* Golgi Apparatus / metabolism* Green Fluorescent Proteins / metabolism HEK293 Cells HeLa Cells Humans Membrane Transport Proteins / metabolism* Mutation Phenotype Phospholipid Transfer Proteins / metabolism* Protein Binding Protein Domains Proteomics Proton-Translocating ATPases / metabolism* RNA Interference Sorting Nexins / metabolism* Transgenes Vesicular Transport Proteins / metabolism* Wnt Proteins / metabolism* |
| IF | 11.878 |
| 引用数 | 11 |
| 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 | tm1320 tm5356 |