Editors' ChoiceCellular Metabolism

Sensing Amino Acids at the Lysosome

Sci. Signal.  13 Jan 2015:
Vol. 8, Issue 359, pp. ec12
DOI: 10.1126/scisignal.aaa6512

The mTORC1 protein kinase is a complex of proteins that functions to regulate growth and metabolism. Activity of mTORC1 is sensitive to the abundance of amino acids, but how the sensing of amino acids is coupled to the control of mTORC1 has been unclear. Wang et al. searched for predicted membrane proteins that interacted with regulators of mTORC1. They identified a protein currently known only as SLC38A9. Interaction of SLC38A9 with mTORC1 regulators was sensitive to the presence of amino acids. SLC38A9 has sequence similarity to amino acid transporters. Effects of modulation of SLC38A9 in cultured human cells indicate that it may be the sensor that connects the abundance of arginine and leucine to mTORC1 activity.

S. Wang, Z.-Y. Tsun, R. L. Wolfson, K. Shen, G. A. Wyant, M. E. Plovanich, E. D. Yuan, T. D. Jones, L. Chantranupong, W. Comb, T. Wang, L. Bar-Peled, R. Zoncu, C. Straub, C. Kim, J. Park, B. L. Sabatini, D. M. Sabatini, Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347, 188–194 (2015). [Abstract] [Full Text]