Giulio Superti-Furga´s group discovered a key component of the nutrients sensing machinery of cells
In order to decide whether to grow and proliferate or to break down and recycle, cells need to sense if the required nutrients are available. A central role in this context is played by the mechanistic target of rapamycin (mTOR) pathway that integrates the presence of growth factors, energy levels, glucose and amino acids to modulate cellular responses, such as protein and lipid synthesis. Past studies have demonstrated that the presence of amino acids is a crucial factor for mTOR activation. Despite this, the precise mechanisms by which amino acid levels are sensed are still poorly understood. In collaboration with Keiryn Bennetts group at CeMM, Lukas Huber and his team at the Biocenter of the Medical University Innsbruck and Cesare Indiveri´s lab at the University of Calabria, the Superti-Furga group with first author Manuele Rebsamen now succeeded in identifying the member 9 of the solute carrier family 38 (SLC38A9) as a key factor, that mediates mTOR activation. The study contributes to elucidate one of the mechanisms by which the cell recognizes the presence of amino acids and thereby controls mTOR activity. Manuele Rebsamen: “SLC38A9 is the first protein to be shown to physically and directly bind both amino acids and the machinery controlling mTOR function, suggesting it could act as sensor. Giulio Superti-Furga: “The finding may lead to new opportunities to interfere with the mTOR pathway by targeting SLC38A9 in situation where aberrant mTOR activation is thought to promote pathological conditions such as cancer and metabolic disorders.”
The study was realized in collaboration with Keiryn Bennett´s group at CeMM, Lukas Huber and his team at the Biocenter of the Medical University Innsbruck and Cesare Indiveri´s lab at the University of Calabria has been published advanced online in Nature, on January 7th, 2015.
The study has been funded by the Austrian Academy of Sciences, European Research Council, European Union, EMBO, Vienna Science and Technology Fund and the Austrian Science Fund, the Italian Ministry of Instruction University and Research.