Characterization of an N-system amino acid transporter expressed in retinaand its involvement in glutamine transport

We report here on the characterization of a mouse N-system amino acid trans porter protein, which is involved in the transport of glutamine. This prote in of 485 amino acids shares 52% sequence homology with an N-system amino a cid transporter, mouse N-system amino acid transporter (mNAT) and its ortho logs. Because this protein shares a high degree of sequence homology and fu nctional similarity to mNAT, we named it mNAT2. mNAT2 is predominately expr essed in the retina and to a slightly lesser extent in the brain. In the re tina, it is located in the axons of ganglion cells in the nerve fiber layer and in the bundles of the optic nerve. Functional analysis of mNAT2 expres sed in Xenopus oocytes revealed that the strongest transport activities wer e specific for L-glutamine. In addition, mNAT2 is a Na+- and pH-dependent, high affinity transporter and partially tolerates substitution of Na+ by Li +. Additionally, mNAT2 functions as a carrier-mediated transporter that fac ilitates efflux. The unique expression pattern and selective glutamine tran sport properties of mNAT2 suggest that it plays a specific role in the upta ke of glutamine involved in the generation of the neurotransmitter glutamat e in retina.