Cloning and expression of a mammalian Na+/amino acid cotransporter with sequence similarity to Na+/glucose cotransporters.

We describe the full-length sequence and functional expression of a cDNA cloned from LLC-PK1 cells, which appears to encode a mammalian Na(+)-dependent neutral amino acid transporter with properties characteristic of system A. This sequence, designated SAAT1, is 76% identical and 89% similar in amino acid sequence to the Na(+)-dependent glucose transporter SGLT1 of the same species. A leucine zipper region was detected in both SAAT1 and SGLT1. The message for SAAT1 was a single 2.4-kilobase species in kidney, but mRNA species of 2.4 and 3.7 kilobases were observed in LLC-PK1 cells as well as in intestine. Transcripts were also found in spleen, liver, and muscle. Expression of SAAT1 in COS-7 cells resulted in increased levels of Na(+)-dependent uptake of 2-(methylamino)isobutyric acid, a specific substrate for the system A amino acid transporter. Uptake due to cDNA expression was inhibited by a range of amino acids that are transported by system A and exhibited a km of 0.8 +/- 0.2 mM. These results suggest that the system A amino acid transporter is closely related to the Na+/glucose transporter SGLT1.