T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control

The uniporter TAT1 (Slc16a10) mediates the facilitated diffusion of aromatic amino acids across basolateral membranes of kidney, small intestine and liver epithelial cells and across the plasma membrane of non-epithelial cells like skeletal myocytes. Its role for body amino acid homeostasis was now investigated using newly generated TAT1 (Slc16a10) defective mice (tat1-/-). These mice grow and reproduce normally, show no gross phenotype and no obvious neurological defect. Histological analysis did not reveal abnormalities and there is no compensatory change in any tested amino acid transporter mRNA. TAT1 null mice display however increased plasma, muscle and kidney aromatic amino acid concentration under both normal and high protein diet, although this concentration remains normal in liver. A major aromatic aminoaciduria and a smaller urinary loss of all substrates additionally transported by L-type amino acid antiporter Lat2-4F2hc (Slc7a8) were revealed under high protein diet. This suggests an epithelial transport defect as also shown by the accumulation of intravenously injected 123I-2-I-L-Phe in kidney and of 3H-L-Phe in ex vivo everted gut sac enterocytes. Taken together, these data indicate that the uniporter TAT1 is required to equilibrate the concentration of aromatic amino acids across specific membranes. For instance, it enables hepatocytes to function as sink that controls the extracellular aromatic amino acid concentration. Additionally, it facilitates the release of aromatic amino acids across the basolateral membrane of small intestine and proximal kidney tubule epithelial cells, thereby allowing the efflux of other neutral amino acids presumably via Lat2-4F2hc.