Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1.
Howard Hughes Medical Institute · Whitehead Institute for Biomedical Research · +4 more institutions
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by…
Citation impact
- FWCI
- 47.09
- Percentile
- 100%
- References
- 48
Authors
18- SWShuyu WangCorresponding
Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Allen Institute, Broad Institute
- ZTZhi-Yang TsunCorresponding
Broad Institute, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Allen Institute, Howard Hughes Medical Institute
- RLRachel L. Wolfson
Massachusetts Institute of Technology, Broad Institute, Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Allen Institute
- KSKuang Shen
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Broad Institute, Allen Institute
- GAGregory A. Wyant
Massachusetts Institute of Technology, Allen Institute, Whitehead Institute for Biomedical Research, Broad Institute, Howard Hughes Medical Institute
Topics & keywords
- mTORC1
- Amino acid
- Leucine
- Arginine
- Lysosome
- Amino acid transporter
- Biochemistry
- Transporter