Identification and characterization of an amino acid transporter expresseddifferentially in liver

Cellular metabolic needs are fulfilled by transport of amino acids across t he plasma membrane by means of specialized transporter proteins. Although m any of the classical amino acid transporters have been characterized functi onally, less than half of these proteins have been cloned. In this report, we identify and characterize a cDNA encoding a plasma membrane amino acid t ransporter. The deduced amino acid sequence is 505 residues and is highly h ydrophobic with the likely predicted structure of 9 transmembrane domains, which putatively place the amino terminus in the cytoplasm and the carboxy terminus on the cell surface. Expression of the cRNA in Xenopus laevis oocy tes revealed strong transport activities specific for histidine and glutami ne. This protein is a Na+- and pH-dependent transporter and tolerates subst itution of Na+ by Li+. Furthermore, this transporter is not an obligatory e xchanger because efflux occurs in the absence of influx. This transporter i s expressed predominantly in the liver, although it is also present in the kidney, brain, and heart. In the liver, it is located in the plasma membran e of hepatocytes, and the strongest expression was detected in those adjace nt to the central vein, gradually decreasing towards the portal tract. Beca use this protein displays functional similarities to the N-system amino aci d transport, we have termed it mNAT, for murine N-system amino acid transpo rter. This is the first transporter gene identified within the N-system, on e of the major amino acid transport systems in the body. The expression pat tern displayed by mNAT suggests a potential role in hepatocyte physiology.