Role of amino acid transporters in amino acid sensing

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 ext...

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Veröffentlicht in:The American journal of clinical nutrition Jg. 99; H. 1; S. 223S
1. Verfasser: Taylor, Peter M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.01.2014
Schlagworte:
Amino Acid Transport Systems - genetics
Amino Acid Transport Systems - metabolism
Amino Acids - metabolism
Animals
Cell Membrane - genetics
Cell Membrane - metabolism
Epithelial Cells - metabolism
Humans
Leucine
Lymphocytes - metabolism
Lysosomes - metabolism
Mammals - metabolism
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Muscle, Skeletal - metabolism
Signal Transduction
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Up-Regulation
ISSN:1938-3207, 1938-3207
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Zusammenfassung: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.
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ISSN:1938-3207
1938-3207
DOI:10.3945/ajcn.113.070086