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Cooperation of Basolateral Epithelial Amino Acid Transporters TAT1 and LAT2 Investigated in a Double Knockout Mouse Model
Author(s) -
Boiadjieva Emilia,
Vilches Clara,
Bodoy Susanna,
Oparija Lalita,
Jando Julia,
Nunes Virginia,
Verrey François,
Palacin Manuel
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.969.4
Subject(s) - efflux , transporter , chemistry , amino acid , amino acid transporter , epithelial polarity , small intestine , biochemistry , membrane transport protein , kidney , biology , endocrinology , gene , cell
Basolateral efflux is a crucial step for amino acid (AA) (re)absorption across small intestine and kidney proximal tubule epithelia mediated by various transporters. There are uniporters that mediate the facilitated diffusion of essential AAs, as does for instance aromatic AA transporter TAT1 (Slc16a10) and also antiporters such as LAT2‐4F2hc (SLC7A8‐SLC3A2) that exchanges neutral AAs. To test the hypothesis that the recycling of aromatic AAs via TAT1 allows the vectorial efflux of other AAs via obligatory exchanger LAT2‐4F2hc, LAT2 ‐/‐ TAT1 ‐/‐ double knockout (dKO) mice were generated. These mice have a reduced body weight (~‐17% at 3 months) but no other overt phenotypic alteration. Under normal protein diet, they excrete in the urine, compared to LAT2 ‐/‐ and TAT1 ‐/‐ knockout mice, higher amounts of aromatic AAs and of some other AAs that are not substrates of TAT1. The amino aciduria was further increased under high protein diet and involved all proteogenic AAs but some charged ones. Screening the mRNA levels of ~20 AA transporters in the kidney suggested a trend of compensatory changes as the level of the transcript of 5 basolateral AA transporters was increased in dKO mice under high protein diet. Preliminary transport experiments with small intestine gut sacs confirm the alteration of transepithelial transport. These observations support the hypothesis that the basolateral efflux of LAT2 substrates depends on the recycling of aromatic AAs via TAT1. Supported by Swiss National Science Foundation.