Cloning and functional characterization of a new subtype of the amino acid transport system N

• Published in: American Journal of Physiology: Cell Physiology 2001-12, Vol.281 (6), p.C1757-C1768
• Main Authors: Nakanishi, Takeo, Kekuda, Ramesh, Fei, You-Jun, Hatanaka, Takahiro, Sugawara, Mitsuru, Martindale, Robert G, Leibach, Frederick H, Prasad, Puttur D, Ganapathy, Vadivel
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Transport Systems, Basic - genetics; Amino Acid Transport Systems, Basic - metabolism; Amino Acid Transport Systems, Neutral; Amino Acids - metabolism; Amino Acids - pharmacology; Animals; Brain Chemistry; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cloning, Molecular; Humans; Membrane Transport Proteins; Molecular Sequence Data; Oocytes - drug effects; Oocytes - physiology; Patch-Clamp Techniques; Peptide Transporter 1; Pigment Epithelium of Eye - cytology; Pigment Epithelium of Eye - metabolism; Protein Isoforms; Rats; Sequence Alignment; Sodium Chloride - pharmacology; Substrate Specificity; Symporters; Tissue Distribution; Xenopus laevis
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.281.6.c1757

Departments of 1  Biochemistry and Molecular Biology, 3  Obstetrics and Gynecology, and 2  Surgery, Medical College of Georgia, Augusta, Georgia 30912 We have cloned a new subtype of the amino acid transport system N2 (SN2 or second subtype of system N) from rat brain. Rat SN2 consists of 471 amino acids and belongs to the recently identified glutamine transporter gene family that consists of system N and system A. Rat SN2 exhibits 63% identity with rat SN1. It also shows considerable sequence identity (50-56%) with the members of the amino acid transporter A subfamily. In the rat, SN2 mRNA is most abundant in the liver but is detectable in the brain, lung, stomach, kidney, testis, and spleen. When expressed in Xenopus laevis oocytes and in mammalian cells, rat SN2 mediates Na + -dependent transport of several neutral amino acids, including glycine, asparagine, alanine, serine, glutamine, and histidine. The transport process is electrogenic, Li + tolerant, and pH sensitive. The transport mechanism involves the influx of Na + and amino acids coupled to the efflux of H + , resulting in intracellular alkalization. Proline, -(methylamino)isobutyric acid, and anionic and cationic amino acids are not recognized by rat SN2. system N2; electrogenicity; proton transport; glutamine transporter family