SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1.

Nature (2015-01-07)
Manuele Rebsamen, Lorena Pochini, Taras Stasyk, Mariana E G de Araújo, Michele Galluccio, Richard K Kandasamy, Berend Snijder, Astrid Fauster, Elena L Rudashevskaya, Manuela Bruckner, Stefania Scorzoni, Przemyslaw A Filipek, Kilian V M Huber, Johannes W Bigenzahn, Leonhard X Heinz, Claudine Kraft, Keiryn L Bennett, Cesare Indiveri, Lukas A Huber, Giulio Superti-Furga
RESUMEN

Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H(+)-ATPase. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAFC
L-Glutamine Solution 200 mM, 29.23 mg/mL in saline, solution, suitable for cell culture
Sigma-Aldrich
Anti-polyHistidine−Peroxidase antibody, Mouse monoclonal antibody produced in mouse, clone HIS-1, purified from hybridoma cell culture
Sigma-Aldrich
RPMI 1640 Amino Acids Solution (50×), Without L-glutamine, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Anti-HA−Peroxidase antibody, Mouse monoclonal antibody produced in mouse, clone HA-7, purified from hybridoma cell culture
Sigma-Aldrich
Anti-SLC38A9 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-LAMTOR4 antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution