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

• Autores: Manuele Rebsamen, Lorena Pochini, Taras Stasyk, Mariana E. G. de Araujo, Michele Galluccio
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 519, Nº 7544, 2015, págs. 477-481
• Idioma: inglés
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• 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 1-3. 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 4-8. 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.