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. Althoug h the molecular mechanisms responsible for its transport across cell membra nes remain poorly understood, classical amino acid transport system N appea rs particularly important. Using intracellular pH measurements, we have now identified an orphan protein related to a vesicular neurotransmitter trans porter as system N. Functional analysis shows that this protein (SN1) invol ves H+ exchange as well as Na+ cotransport and, under physiological conditi ons, mediates glutamine efflux as well as uptake. Together with the pattern of SN1 expression, these unusual properties suggest novel physiological ro les for system N in nitrogen metabolism and synaptic transmission.