Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission.
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.
Chaudhry
F A
FA
Department of Neurology, UCSF School of Medicine, San Francisco, California 94143-0435, USA.
Reimer
R J
RJ
Krizaj
D
D
Barber
D
D
Storm-Mathisen
J
J
Copenhagen
D R
DR
Edwards
R H
RH
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; C403222:system N protein 1; D005973:Glutamine; D012964:Sodium; D009584:Nitrogen