Publications

• Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N.

  Nakanishi T., Sugawara M., Huang W., Martindale R.G., Leibach F.H., Ganapathy M.E., Prasad P.D., Ganapathy V.

  We have cloned a new subtype of the amino acid transport system N from a human liver cell line. This transporter, designated SN2, consists of 472 amino acids and exhibits 62% identity with human SN1 at the level of amino acid sequence. SN2-specific transcripts are expressed predominantly in the st ... >> More

  We have cloned a new subtype of the amino acid transport system N from a human liver cell line. This transporter, designated SN2, consists of 472 amino acids and exhibits 62% identity with human SN1 at the level of amino acid sequence. SN2-specific transcripts are expressed predominantly in the stomach, brain, liver, lung, and intestinal tract. The sizes of the transcripts vary in different tissues, indicating tissue-specific alternative splicing of the SN2 mRNA. In contrast, SN1 is expressed primarily in the brain and liver and there is no evidence for the presence of multiple transcripts of varying size for SN1. When expressed in mammalian cells, the cloned human SN2 mediates Na(+)-coupled transport of system N-specific amino acid substrates (glutamine, asparagine, and histidine). In addition, SN2 also transports serine, alanine, and glycine. Anionic amino acids, cationic amino acids, imino acids, and N-alkylated amino acids are not recognized as substrates by human SN2. The SN2-mediated transport process is Li(+)-tolerant and highly pH-dependent. The Michaelis-Menten constant for histidine uptake via human SN2 is 0.6 +/-0.1 mM. The gene coding for SN2 is located on human chromosome Xp11.23. Successful cloning of SN2 provides the first molecular evidence for the existence of subtypes within the amino acid transport system N in mammalian tissues. << Less

  Biochem. Biophys. Res. Commun. 281:1343-1348(2001) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Coupled and uncoupled proton movement by amino acid transport system N.

  Chaudhry F.A., Krizaj D., Larsson P., Reimer R.J., Wreden C., Storm-Mathisen J., Copenhagen D., Kavanaugh M., Edwards R.H.

  The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and gamma-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conducta ... >> More

  The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and gamma-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conductance activated by glutamine, and this conductance is selective for H(+). Although SN1 couples amino acid uptake to H(+) exchange, the glutamine-gated H(+) conductance is not stoichiometrically coupled to transport. Protons thus permeate SN1 both coupled to and uncoupled from amino acid flux, providing novel mechanisms to regulate the transfer of glutamine between cells. << Less

  EMBO J. 20:7041-7051(2001) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission.

  Chaudhry F.A., Reimer R.J., Krizaj D., Barber D., Storm-Mathisen J., Copenhagen D.R., Edwards R.H.

  The amino acid glutamine has a central role in nitrogen metabolism. Although the molecular mechanisms responsible for its transport across cell membranes remain poorly understood, classical amino acid transport system N appears particularly important. Using intracellular pH measurements, we have n ... >> More

  The amino acid glutamine has a central role in nitrogen metabolism. Although the molecular mechanisms responsible for its transport across cell membranes remain poorly understood, classical amino acid transport system N appears particularly important. Using intracellular pH measurements, we have now identified an orphan protein related to a vesicular neurotransmitter transporter as system N. Functional analysis shows that this protein (SN1) involves H+ exchange as well as Na+ cotransport and, under physiological conditions, mediates glutamine efflux as well as uptake. Together with the pattern of SN1 expression, these unusual properties suggest novel physiological roles for system N in nitrogen metabolism and synaptic transmission. << Less

  Cell 99:769-780(1999) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• The system N transporter SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors.

  Hamdani E.H., Gudbrandsen M., Bjoerkmo M., Chaudhry F.A.

  Activation of NMDA receptor requires two co-agonists, glutamate and glycine. Despite its intrinsic role in brain functions molecular mechanisms involved in glutamate replenishment and identification of the origin of glycine have eluded characterization. We have performed direct measurements of gly ... >> More

  Activation of NMDA receptor requires two co-agonists, glutamate and glycine. Despite its intrinsic role in brain functions molecular mechanisms involved in glutamate replenishment and identification of the origin of glycine have eluded characterization. We have performed direct measurements of glycine flux by SN2 (Slc38a5; also known as SNAT5), executed extensive electrophysiological characterization as well as implemented ratiometric analyses to show that SN2 transport resembles SN1 in mechanism but differ in functional implications. We report that rat SN2 mediates electroneutral and bidirectional transport of glutamine and glycine at perisynaptic astroglial membranes. Sophisticated coupled and uncoupled movements of H(+) differentially associate with glutamine and glycine transport by SN2 and regulate pH(i) and the release mode of the transporter. Consequently, SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors. << Less

  Glia 60:1671-1683(2012) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.