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

Content Provider	PubMed Central
Author	Luca, Mariotta Ramadan, Tamara Singer, Dustin Adriano, Guetg Herzog, Brigitte Stoeger, Claudia Manuel, Palacín Tony, Lahoutte Camargo, Simone M. R. Verrey, François
Copyright Year	2012
Abstract	The uniporter TAT1 (Slc16a10) mediates the facilitated diffusion of aromatic amino acids (AAAs) 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 AA homeostasis has now been 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 AA transporter mRNA. TAT1 null mice, however, display increased plasma, muscle and kidney AAA concentration under both normal and high protein diet, although this concentration remains normal in the liver. A major aromatic aminoaciduria and a smaller urinary loss of all substrates additionally transported by l-type AA antiporter Lat2–4F2hc (Slc7a8) were revealed under a 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 l-[3H]Phe in ex vivo everted gut sac enterocytes. Taken together, these data indicate that the uniporter TAT1 is required to equilibrate the concentration of AAAs across specific membranes. For instance, it enables hepatocytes to function as a sink that controls the extracellular AAAs concentration. Additionally, it facilitates the release of AAAs across the basolateral membrane of small intestine and proximal kidney tubule epithelial cells, thereby allowing the efflux of other neutral AAs presumably via Lat2–4F2hc.
Related Links	http://dx.doi.org/10.1113/jphysiol.2012.239574
Ending Page	6424
Page Count	12
Starting Page	6413
File Format	PDF
ISSN	14697793
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 24
Volume Number	590
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2012-12-15
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

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