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 B(0)AT1 (slc6a19) and was hence named B(0)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 microM. 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 B(0)AT2 was Na+-dependent, Cl--independent and electrogenic. Superfusion of mouse B(0)AT2-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 B(0)AT2-like transport activity was detected in synaptosomes and cultured neurons. A potential role of B(0)AT2 in transporting neurotransmitter precursors and neuromodulators is proposed.
Bröer
Angelika
A
School of Biochemistry & Molecular Biology, Australian National University, Canberra, ACT 0200, Australia.
Tietze
Nadine
N
Kowalczuk
Sonja
S
Chubb
Sarah
S
Munzinger
Michael
M
Bak
Lasse K
LK
Bröer
Stefan
S
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021542:Amino Acids, Neutral / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D003001:Cloning, Molecular; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011487:Protein Conformation; D012964:Sodium / Q000494:pharmacology*; D013379:Substrate Specificity; D013574:Synaptosomes / Q000378:metabolism
D026921:Amino Acid Transport Systems, Neutral; D021542:Amino Acids, Neutral; C505021:SLC6A19 protein, mouse; C508691:Slc6a15 protein, mouse; D011392:Proline; D012964:Sodium