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

Abstract

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 B0AT2. Leucine, isoleucine, valine, proline and methionine were recognized by the transporter, with values of K0.5 (half-saturation constant) ranging from 40 to 200 μM. Alanine, glutamine and phenylalanine were low-affinity substrates of the transporter, with K0.5 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 K0.5 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.