Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle.
Glutamine is involved in a variety of metabolic processes, including recycling of the neurotransmitters glutamate and gamma-aminobutyric acid (GABA). The system N transporter SN1 mediates efflux as well as influx of glutamine in glial cells [Chaudhry et al. (1999), Cell, 99, 769-780]. We here report qualitative and quantitative data on SN1 protein expression in rat. The total tissue concentrations of SN1 in brain and in kidney are half and one-quarter, respectively, of that in liver, but the average concentration of SN1 could be higher in astrocytes than in hepatocytes. Light and electron microscopic immunocytochemistry shows that glutamatergic, GABAergic and, surprisingly, purely glycinergic boutons are ensheathed by astrocytic SN1 laden processes, indicating a role of glutamine in the production of all three rapid transmitters. A dedication of SN1 to neurotransmitter recycling is further supported by the lack of SN1 immunoreactivity in oligodendrocytes (cells rich in glutamine but without perisynaptic processes). All neuronal structures appear unlabelled implying that a different protein mediates glutamine uptake into nerve endings. In several regions, SN1 immunoreactivity is higher in association with GABAergic than glutamatergic synapses, in agreement with observations that exogenous glutamine increases output of transmitter glutamate but not GABA. Nerve terminals with low transmitter reuptake or high prevailing firing frequency are associated with high SN1 immunoreactivity in adjacent glia. Bergmann glia and certain other astroglia contain very low levels of SN1 immunoreactivity compared to most astroglia, including retinal Müller cells, indicating the possible existence of SN isoforms and alternative mechanisms for transmitter recycling.
Boulland
Jean-Luc
JL
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105 Blindern, Norway.
Osen
Kirsten K
KK
Levy
Line M
LM
Danbolt
Niels Christian
NC
Edwards
Robert H
RH
Storm-Mathisen
Jon
J
Chaudhry
Farrukh A
FA
D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000502:physiology*; D005998:Glycine / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D026921:Amino Acid Transport Systems, Neutral; D026901:Membrane Transport Proteins; C403222:system N protein 1; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine