PerspectiveCell Biology

Making sense of amino acid sensing

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Science  09 Jan 2015:
Vol. 347, Issue 6218, pp. 128-129
DOI: 10.1126/science.aaa4570

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Summary

Mammalian cells integrate nutrient and growth factor availability with anabolic responses to support cell growth and proliferation. A key signaling hub in this process is the mechanistic target of rapamycin complex 1 (mTORC1) (1, 2). Growth factor receptors deliver activating signals to mTORC1 primarily through the phosphoinositide 3-kinase (PI3K)–AKT signaling cascade. However, amino acid sufficiency activates mTORC1 through a family of guanosine triphosphatases (GTPases) called Rags (3, 4). The lysosome is now recognized as a key intracellular organelle involved in mTORC1 activation by amino acids and growth factors (5). A candidate amino acid sensor for lysosome-based activation of mTORC1 has now been identified by Wang et al. (6) on page 188 of this issue, and by Rebsamen et al. (7). However, studies by Thomas et al. (8), and by Jewell et al. (9) on page 194 of this issue, demonstrate that amino acid sensing is not the sole domain of either the lysosome or its associated Rag GTPases. These four studies advance substantially our understanding of the amino acid–sensing machinery in mammalian cells.