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Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses.

ABSTRACT: SLC38A6 is one of the newly found members of the solute carrier 38 family consisting of total 11 members, of which only 6 have been characterized so far. Being the only glutamine transporter family expressed in the brain, this family of proteins are most probably involved in the regulation of the glutamate-glutamine cycle, responsible for preventing excitotoxicity. We used immunohistochemistry to show that SLC38A6 is primarily expressed in excitatory neurons and is not expressed in the astrocytes. Using proximity ligation assay, we have quantified the interactions of this SLC38 family protein with other proteins with known localization in the cells, showing that this transporter is expressed at the synapses. Moreover, this study has enabled us to come up with a model suggesting sub-cellular localization of SLC38A6 at the synaptic membrane of the excitatory neurons.

SUBMITTER: Bagchi S

PROVIDER: S-EPMC3994050 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses.

Bagchi Sonchita S Baomar Hajar Ali HA Al-Walai Somar S Al-Sadi Saifaddin S Fredriksson Robert R

PloS one 20140421 4

SLC38A6 is one of the newly found members of the solute carrier 38 family consisting of total 11 members, of which only 6 have been characterized so far. Being the only glutamine transporter family expressed in the brain, this family of proteins are most probably involved in the regulation of the glutamate-glutamine cycle, responsible for preventing excitotoxicity. We used immunohistochemistry to show that SLC38A6 is primarily expressed in excitatory neurons and is not expressed in the astrocyte ...[more]

PMID: 24752331

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Project description:A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses - those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.

Dataset Information

Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses.

Publications

Histological analysis of SLC38A6 (SNAT6) expression in mouse brain shows selective expression in excitatory neurons with high expression in the synapses.

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