論文 - 詳細
| RRC ID | 32502 |
|---|---|
| 著者 | Gleixner EM, Canaud G, Hermle T, Guida MC, Kretz O, Helmstädter M, Huber TB, Eimer S, Terzi F, Simons M. |
| タイトル | V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. |
| ジャーナル | Cell Rep |
| Abstract |
mTOR kinase is a master growth regulator that can be stimulated by multiple signals, including amino acids and the lysosomal small GTPase Rheb. Recent studies have proposed an important role for the V-ATPase in the sensing of amino acids in the lysosomal lumen. Using the Drosophila wing as a model epithelium, we show here that the V-ATPase is required for Rheb-dependent epithelial growth. We further uncover a positive feedback loop for the control of apical protein uptake that depends on V-ATPase/mTOR signaling. This feedback loop includes Rheb-dependent transcriptional regulation of the multiligand receptor Megalin, which itself is required for Rheb-induced endocytosis. In addition, we provide evidence that long-term mTOR inhibition with rapamycin in mice causes reduction of Megalin levels and proteinuria in the proximal tubular epithelium of the kidney. Thus, our findings unravel a homeostatic mechanism that allows epithelial cells to promote protein uptake under normal conditions and to prevent uptake in lysosomal stress conditions. |
| 巻・号 | 8(1) |
| ページ | 10-9 |
| 公開日 | 2014-7-10 |
| DOI | 10.1016/j.celrep.2014.05.035 |
| PII | S2211-1247(14)00429-X |
| PMID | 24953654 |
| MeSH | Animals Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Endocytosis* Epithelium / growth & development Epithelium / metabolism Feedback, Physiological Low Density Lipoprotein Receptor-Related Protein-2 / genetics Low Density Lipoprotein Receptor-Related Protein-2 / metabolism* Male Mice Mice, Inbred C57BL Monomeric GTP-Binding Proteins / genetics Monomeric GTP-Binding Proteins / metabolism Neuropeptides / genetics Neuropeptides / metabolism Proteinuria / metabolism Ras Homolog Enriched in Brain Protein Signal Transduction TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / metabolism* Vacuolar Proton-Translocating ATPases / genetics Vacuolar Proton-Translocating ATPases / metabolism* |
| IF | 8.109 |
| 引用数 | 29 |
| 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 | 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 | |
| ショウジョウバエ | |