Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle

To date, two different transporters that are capable of transporting α-(methylamino)isobutyric acid, the specific substrate for amino acid transport system A, have been cloned. These two transporters are known as ATA1 and ATA2. We have cloned a third transporter that is able to transport the system A-specific substrate. This new transporter, cloned from rat skeletal muscle and designated rATA3, consists of 547 amino acids and has a high degree of homology to rat ATA1 (47% identity) and rat ATA2 (57% identity). rATA3 mRNA is present only in the liver and skeletal muscle. When expressed in Xenopus laevis oocytes, rATA3 mediates the transport of α-[¹⁴C](methylamino)isobutyric acid and [³H]alanine. With the two-microelectrode voltage clamp technique, we have shown that exposure of rATA3-expressing oocytes to neutral, short-chain aliphatic amino acids induces inward currents. The amino acid-induced current is Na⁺-dependent and pH-dependent. Analysis of the currents with alanine as the substrate has shown that the K_0.5 for alanine (i.e., concentration of the amino acid yielding half-maximal current) is 4.2 ± 0.1 mM and that the Na⁺:alanine stoichiometry is 1:1. (C) 2000 Elsevier Science B.V.