The orphan transporter v7-3 (slc6a15) is a Na⁺-dependent neutral amino acid transporter (B⁰AT2)

Transporters of the SLC6 (solute carrier 6) family play an important role in the removal of neurotransmitters in brain tissue and in amino acid transport in epithelial cells. In the present study, we demonstrate that mouse v7-3 (slc6a15) encodes a transporter for neutral amino acids. The transporter is functionally and sequence related to B⁰AT1 (slc6a19) and was hence named B°AT2. Leucine, isoleucine, valine, proline and methionine were recognized by the transporter, with values of K_0.5 (half-saturation constant) ranging from 40 to 200 μM. Alanine, glutamine and phenylalanine were low-affinity substrates of the transporter, with K_0.5 values in the millimolar range. Transport of neutral amino acids via B⁰AT2 was Na⁺-dependent, Cl^--independent and electrogenic. Superfusion of mouse B⁰AT2-expressing oocytes with amino acid substrates generated robust inward currents. Na⁺-activation kinetics of proline transport and uptake under voltage clamp suggested a 1:1 Na ⁺/amino acid co-transport stoichiometry. Susbtrate and co-substrate influenced each other's K_0.5 values, suggesting that they share the same binding site. A mouse B⁰AT2-like transport activity was detected in synaptosomes and cultured neurons. A potential role of B⁰AT2 in transporting neurotransmitter precursors and neuromodulators is proposed.