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Regulation of TFEB and V-ATPases by mTORC1

EMBO Journal, ISSN: 0261-4189, Vol: 30, Issue: 16, Page: 3242-3258
2011
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Article Description

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. © 2011 European Molecular Biology Organization.

Bibliographic Details

Peña-Llopis, Samuel; Vega-Rubin-de-Celis, Silvia; Schwartz, Jacob C; Wolff, Nicholas C; Tran, Tram Anh T; Zou, Lihua; Xie, Xian-Jin; Corey, David R; Brugarolas, James

Springer Science and Business Media LLC

Neuroscience; Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology

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