Basolateral aromatic amino acid transporter TAT1 (Slc16a10) functions as an efflux pathway.
Basolateral efflux is a necessary step in transepithelial (re)absorption of amino acids from small intestine and kidney proximal tubule. The best characterized basolateral amino acid transporters are y+LAT1-4F2hc and LAT2-4F2hc that function as obligatory exchangers and thus, do not contribute to net amino acid (re)absorption. The aromatic amino acid transporter TAT1 was shown previously to localize basolaterally in rat's small intestine and to mediate the efflux of L-Trp in the absence of exchange substrate, upon expression in Xenopus oocytes. We compared here the amino acid influx and efflux via mouse TAT1 in Xenopus oocytes. The results show that mTAT1 functions as facilitated diffusion pathway for aromatic amino acids and that its properties are symmetrical in terms of selectivity and apparent affinity. We show by real-time RT-PCR that its mRNA is highly expressed in mouse small intestine mucosa, kidney, liver, and skeletal muscle as well as present in all other tested tissues. We show that mTAT1 is not N-glycosylated and that it localizes to the mouse kidney proximal tubule. This expression is characterized by an axial gradient similar to that of the luminal neutral amino acid transporter B0AT1 and shows the same basolateral localization as 4F2hc. mTAT1 also localizes to the basolateral membrane of small intestine enterocytes and to the sinusoidal side of perivenous hepatocytes. In summary, we show that TAT1 is a basolateral epithelial transporter and that it can function as a net efflux pathway for aromatic amino acids. We propose that it, thereby, may supply parallel exchangers with recycling uptake substrates that could drive the efflux of other amino acids.
Ramadan
Tamara
T
Institute of Physiology and Centre for Integrative Human Physiology (ZIHP), University of Zürich, Winterthurerstrasse, Zürich, Switzerland.
Camargo
Simone M R
SM
Summa
Vanessa
V
Hunziker
Peter
P
Chesnov
Serge
S
Pos
Klaas M
KM
Verrey
Francois
F
D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D005455:Fluorescent Antibody Technique; D007421:Intestine, Small / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes; D010649:Phenylalanine / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D013347:Subcellular Fractions; D014018:Tissue Distribution; D014982:Xenopus laevis
D026921:Amino Acid Transport Systems, Neutral; D024322:Amino Acids, Aromatic; D027283:Large Neutral Amino Acid-Transporter 1; D012333:RNA, Messenger; C509612:Slc16a10 protein, mouse; D010649:Phenylalanine