Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1
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Author(s)
Comb, William C.
Schweitzer, Lawrence David
Bar-Peled, Liron
Sabatini, David
Date Issued
August 2015
Journal
Cell Reports
Publisher
Elsevier
Citation
Schweitzer, Lawrence D.; Comb, William C.; Bar-Peled, Liron and Sabatini, David M. “Disruption of the Rag-Ragulator Complex by C17orf59 Inhibits mTORC1.” Cell Reports 12, no. 9 (September 2015): 1445–1455. © 2015 The Authors
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Author's final manuscript
Abstract
mTORC1 controls key processes that regulate cell growth, including mRNA translation, ribosome biogenesis, and autophagy. Environmental amino acids activate mTORC1 by promoting its recruitment to the cytosolic surface of the lysosome, where its kinase is activated downstream of growth factor signaling. mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the lysosomal membrane by Ragulator, a lysosome-bound scaffold. Here, we identify c17orf59 as a Ragulator-interacting protein that regulates mTORC1 activity through its interaction with Ragulator at the lysosome. The binding of c17orf59 to Ragulator prevents Ragulator interaction with the Rag GTPases, both in cells and in vitro, and decreases Rag GTPase lysosomal localization. Disruption of the Rag-Ragulator interaction by c17orf59 impairs mTORC1 activation by amino acids by preventing mTOR from reaching the lysosome. By disrupting the Rag-Ragulator interaction to inhibit mTORC1, c17orf59 expression may represent another mechanism to modulate nutrient sensing by mTORC1.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.07.052
