SLC38A9 is a Component of the Lysosomal Amino Acid Sensing Machinery That Controls MTORC1

Overview

Journal Nature

Specialty Science

Date 2015 Jan 7

PMID 25561175

Citations 367

Authors

Manuele Rebsamen

Lorena Pochini

Taras Stasyk

Mariana E G de Araujo

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

Affiliations

Soon will be listed here.

Abstract

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.

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