Document Detail

T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control.
MedLine Citation:
PMID:  23045339     Owner:  NLM     Status:  MEDLINE    
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 (123)I-2-I-l-Phe in kidney and l-[(3)H]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.
Luca Mariotta; Tamara Ramadan; Dustin Singer; Adriano Guetg; Brigitte Herzog; Claudia Stoeger; Manuel Palacín; Tony Lahoutte; Simone M R Camargo; François Verrey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-06-13     Revised Date:  2013-12-18    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  6413-24     Citation Subset:  IM    
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MeSH Terms
Amino Acid Transport System y+ / metabolism
Amino Acid Transport Systems, Neutral / deficiency,  genetics,  metabolism*
Amino Acids, Aromatic / blood,  metabolism*
Antigens, CD98 Heavy Chain / metabolism
Antigens, CD98 Light Chains / metabolism
Dietary Proteins / blood,  metabolism*
Epithelial Cells / metabolism
Intestine, Small / metabolism
Kidney / metabolism
Liver / metabolism
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal / metabolism
RNA, Messenger / metabolism
Reg. No./Substance:
0/Amino Acid Transport System y+; 0/Amino Acid Transport Systems, Neutral; 0/Amino Acids, Aromatic; 0/Antigens, CD98 Heavy Chain; 0/Antigens, CD98 Light Chains; 0/Dietary Proteins; 0/RNA, Messenger; 0/SLC7A8 protein, mouse; 0/Slc16a10 protein, mouse; 0/Slc3A2 protein, mouse
Comment In:
J Physiol. 2012 Dec 15;590(Pt 24):6255-6   [PMID:  23241921 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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