title: T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control.
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 (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.
authors.affiliation: Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Mariotta
authors.forename: Tamara
authors.initials: T
authors.lastname: Ramadan
authors.forename: Dustin
authors.initials: D
authors.lastname: Singer
authors.forename: Adriano
authors.initials: A
authors.lastname: Guetg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Herzog
authors.forename: Claudia
authors.initials: C
authors.lastname: Stoeger
authors.forename: Manuel
authors.initials: M
authors.lastname: Palacín
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
authors.forename: Simone M R
authors.initials: SM
authors.lastname: Camargo
authors.forename: François
authors.initials: F
authors.lastname: Verrey
mesh_terms: D027182:Amino Acid Transport System y+ / Q000378:metabolism; D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024322:Amino Acids, Aromatic / Q000097:blood / Q000378:metabolism*; D000818:Animals; D004044:Dietary Proteins / Q000097:blood / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism; D005838:Genotype; D006706:Homeostasis; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D027182:Amino Acid Transport System y+; D026921:Amino Acid Transport Systems, Neutral; D024322:Amino Acids, Aromatic; D004044:Dietary Proteins; D027282:Fusion Regulatory Protein 1, Heavy Chain; D027301:Fusion Regulatory Protein 1, Light Chains; D012333:RNA, Messenger; C518286:SLC7A8 protein, mouse; C509612:Slc16a10 protein, mouse; C523212:Slc3A2 protein, mouse