| First Author | Peña-Llopis S | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 16 | Pages | 3242-58 |
| PubMed ID | 21804531 | Mgi Jnum | J:175613 |
| Mgi Id | MGI:5286768 | Doi | 10.1038/emboj.2011.257 |
| Citation | Pena-Llopis S, et al. (2011) Regulation of TFEB and V-ATPases by mTORC1. EMBO J 30(16):3242-58 |
| abstractText | Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is an important, highly conserved, regulator of cell growth. Ancient among the signals that regulate mTORC1 are nutrients. Amino acids direct mTORC1 to the surface of the late endosome/lysosome, where mTORC1 becomes receptive to other inputs. However, the interplay between endosomes and mTORC1 is poorly understood. Here, we report the discovery of a network that links mTORC1 to a critical component of the late endosome/lysosome, the V-ATPase. In an unbiased screen, we found that mTORC1 regulated the expression of, among other lysosomal genes, the V-ATPases. mTORC1 regulates V-ATPase expression both in cells and in mice. V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB. TFEB is required for the expression of a large subset of mTORC1 responsive genes. mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis. These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis. |
