title: Role of amino acid transporters in amino acid sensing.
abstract: Amino acid (AA) transporters may act as sensors, as well as carriers, of tissue nutrient supplies. This review considers recent advances in our understanding of the AA-sensing functions of AA transporters in both epithelial and nonepithelial cells. These transporters mediate AA exchanges between extracellular and intracellular fluid compartments, delivering substrates to intracellular AA sensors. AA transporters on endosomal (eg, lysosomal) membranes may themselves function as intracellular AA sensors. AA transporters at the cell surface, particularly those for large neutral AAs such as leucine, interact functionally with intracellular nutrient-signaling pathways that regulate metabolism: for example, the mammalian target of rapamycin complex 1 (mTORC1) pathway, which promotes cell growth, and the general control non-derepressible (GCN) pathway, which is activated by AA starvation. Under some circumstances, upregulation of AA transporter expression [notably a leucine transporter, solute carrier 7A5 (SLC7A5)] is required to initiate AA-dependent activation of the mTORC1 pathway. Certain AA transporters may have dual receptor-transporter functions, operating as "transceptors" to sense extracellular (or intracellular) AA availability upstream of intracellular signaling pathways. New opportunities for nutritional therapy may include targeting of AA transporters (or mechanisms that upregulate their expression) to promote protein-anabolic signals for retention or recovery of lean tissue mass.
authors.affiliation: Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Taylor
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics* / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007930:Leucine; D008214:Lymphocytes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007930:Leucine