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Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1.

Science (New York, N.Y.) (2015-01-09)
Shuyu Wang, Zhi-Yang Tsun, Rachel L Wolfson, Kuang Shen, Gregory A Wyant, Molly E Plovanich, Elizabeth D Yuan, Tony D Jones, Lynne Chantranupong, William Comb, Tim Wang, Liron Bar-Peled, Roberto Zoncu, Christoph Straub, Choah Kim, Jiwon Park, Bernardo L Sabatini, David M Sabatini
RESUMEN

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 amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.

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Sigma-Aldrich
L-arginina, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
SAFC
L-arginina
Sigma-Aldrich
Hexokinase from Saccharomyces cerevisiae, Type F-300, lyophilized powder, ≥130 units/mg protein (biuret)
Sigma-Aldrich
L-arginina, reagent grade, ≥98%
Sigma-Aldrich
L-arginina, 99%, FCC, FG
Sigma-Aldrich
L-arginina, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Hexokinase from Saccharomyces cerevisiae, lyophilized powder, ≥350 units/mg protein, Protein ≥10 % by biuret
Supelco
L-arginina, Pharmaceutical Secondary Standard; Certified Reference Material
L-arginina, European Pharmacopoeia (EP) Reference Standard