The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1
Author(s)Spooner, Eric; Tsun, Zhi-Yang; Bar-Peled, Liron; Chantranupong, Lynne; Zoncu, Roberto; Wang, Tim; Kim, Choah; Sabatini, David; ... Show more Show less
MetadataShow full item record
The mTORC1 kinase is a master growth regulator that senses numerous environmental cues, including amino acids. The Rag GTPases interact with mTORC1 and signal amino acid sufficiency by promoting the translocation of mTORC1 to the lysosomal surface, its site of activation. The Rags are unusual GTPases in that they function as obligate heterodimers, which consist of RagA or B bound to RagC or D. While the loading of RagA/B with GTP initiates amino acid signaling to mTORC1, the role of RagC/D is unknown. Here, we show that RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP bound for the interaction to occur. We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a molecular function for the FLCN tumor suppressor.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research; Koch Institute for Integrative Cancer Research at MIT
Tsun, Zhi-Yang; Bar-Peled, Liron; Chantranupong, Lynne; Zoncu, Roberto; Wang, Tim; Kim, Choah; Spooner, Eric and Sabatini, David M. "The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1." Molecular Cell 52, no. 4 (November 2013): 495-505 © 2013 Elsevier Inc
Author's final manuscript