Reference - Detail
| RRC ID | 32502 |
|---|---|
| Author | Gleixner EM, Canaud G, Hermle T, Guida MC, Kretz O, Helmstädter M, Huber TB, Eimer S, Terzi F, Simons M. |
| Title | V-ATPase/mTOR signaling regulates megalin-mediated apical endocytosis. |
| Journal | 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. |
| Volume | 8(1) |
| Pages | 10-9 |
| Published | 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 |
| Times Cited | 29 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | |