SAT1, a glutamine transporter, is preferentially expressed in GABAergic neurons

Abstract

Subsets of GABAergic neurons are able to maintain high frequency discharge patterns, which requires efficient replenishment of the releasable pool of GABA. Although glutamine is considered a preferred precursor of GABA, the identity of transporters involved in glutamine uptake by GABAergic neurons remains elusive. Molecular analyses revealed that SAT1 (Slc38a1) features system A characteristics with a preferential affinity for glutamine, and that SAT1 mRNA expression is associated with GABAergic neurons. By generating specific antibodies against SAT1 we show that this glutamine carrier is particularly enriched in GABAergic neurons. Cellular SAT1 distribution resembles that of GAD67, an essential GABA synthesis enzyme, suggesting that SAT1 can be involved in translocating glutamine into GABAergic neurons to facilitate inhibitory neurotransmitter generation.

Protein Kinase C-Mediated Phosphorylation of a Single Serine Residue on the Rat Glial Glutamine Transporter SN1 Governs Its Membrane Trafficking

“…We now demonstrate that SN1 after its retrieval from the plasma membrane is targeted to the intracellular stores in which some of it may be colocalized with the TGN marker syntaxin 6. A reserve pool of the homologous system A transporters SAT1 and SAT2, acting on the neuronal membranes, is also colocalized with syntaxin 6 and shown to be recruited to the plasma membranes during hormonal stimulation (Hatanaka et al, 2006;Solbu et al, 2010). Glutamate is accumulated in synaptic vesicles through the action of vesicular glutamate transporters (VGLUT1/-2/-3).…”

“…According to the prevailing hypothesis, a significant amount of released glutamate and GABA is transported into perisynaptic astroglial processes, converted to glutamine, and then transported back to neurons for transmitter regeneration (Albrecht et al, 2007). Existence of such a glutamate/GABA-glutamine cycle has been bolstered by the characterization of a family of system A and system N transporters: SAT1 (Slc38a1) and SAT2 (Slc38a2) are selectively enriched in GABAergic and glutamatergic neurons, respectively, and inhibition of system A transport inhibits neuronal transmitter generation and synaptic transmission Liang et al, 2006;Jenstad et al, 2009;Solbu et al, 2010). System N transporter SN1, selectively expressed on astroglial processes ensheathing synapses, mediates release of glutamine and furnishes neurons with the primary neurotransmitter precursor (Chaudhry et al, 1999(Chaudhry et al, , 2001Boulland et al, 2002).…”

Cracking Down on Inhibition: Selective Removal of GABAergic Interneurons from Hippocampal Networks

“…Since SAVA infusion might affect parvalbumin's expressional control ("marker drop-out") rather than the physical elimination of parvalbumin ϩ neurons from the CA1 subfield, we mapped the distribution of GAD67 (Asada et al, 1997) and SAT1, an alternative neurochemical marker of parvalbumin ϩ basket cells (Solbu et al, 2010). The loss of GAD67 and SAT1 was found comparable to that of parvalbumin upon SAVA but not unc-Ab infusion (Fig.…”

“…Sections were the exposed to select combinations of the following primary antibodies (in PB also containing 1% NDS and 0.2% Triton X-100 for 48 -72 h at 4°C): guinea pig anti-parvalbumin (1:300, Synaptic Systems), rabbit anti-parvalbumin (1: 2000, Swant), biotinylated rabbit anti-parvalbumin (20 g/ml; Synaptic Systems), rabbit anti-system A transporter 1 (SAT1, 1:1000) (Solbu et al, 2010), goat anti-CB 1 cannabinoid receptor (CB 1 R, 1:1000) (Kawamura et al, 2006), rabbit anti-VGLUT1 (1:2000, Synaptic Systems), guinea pig anti-VGLUT1 (1:1000) (Kaneko et al, 2002), guinea pig anti-vesicular glutamate transporter 3 (VGLUT3, 1:1000) (Hioki et al, 2004), goat anti-calretinin (1:1000; Swant), mouse anti-calbindin D28k (CB, 1:1000; Swant), rabbit anti-GABA A receptor ␣1 subunit (5 g/ml) (Fritschy et al, 1992), mouse anti-GAD67 (1:5000; Millipore Bioscience Research Reagents), rabbit antineuropeptide Y (1:400, Diasorin), rabbit anti-somatostatin (1:400, Acris), guinea pig anti-GFAP (1:400, Synaptic Systems), rabbit anti-ionized Ca 2ϩ -binding protein adaptor molecule 1 (Iba-1; 1:200, Wako) and biotinylated mouse anti-neuronal nuclei (NeuN; 20 g/ml; Millipore Bioscience Research Reagents). After extensive rinsing in PB, immunoreactivities were revealed by carbocyanine (Cy) 2, 3 or 5-tagged secondary antibodies raised in donkey [1:200 (Jackson ImmunoResearch), 2 h at 22Ϫ24°C].…”

Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy

“…electrogenic in nature constituting the driving force for the amino acid uptake (Chaudhry et al, 2002). SAT1 is expressed in the somatodendrites of neurons in brain regions enriched in GABAergic neurons, and its proximity to VGAT, the vesicular GABA transporter indicates that it might be related to glutamine uptake as a prerequisite to replenish the GABA neurotransmitter pool (Solbu et al, 2010;Varoqui et al, 2000). SAT2 is more ubiquitously expressed, being found localized mainly in somatodendrites and axons of glutamatergic neurons Jenstad et al, 2009).…”