Abstract
In brain cells, glutamine transporters are vital to monitor and control the levels of glutamate and GABA. There are 11 members of the SLC38 family of amino acid transporters of which eight have been functionally characterized. Here, we report the first histological and functional characterization of the previously orphan member, SLC38A10. We used pairwise global sequence alignments to determine the sequence identity between the SLC38 family members. SLC38A10 was found to share 20–25% transmembrane sequence identity with several family members, and was predicted to have 11 transmembrane helices. SLC38A10 immunostaining was abundant in mouse brain using a custom‐made anti‐SLC38A10 antibody and colocalization of SLC38A10 immunoreactivity with markers for neurons and astrocytes was detected. Using Xenopus laevis oocytes overexpressing SLC38A10, we show that SLC38A10 mediates bidirectional transport of l‐glutamine, l‐alanine, l‐glutamate, and d‐aspartate, and efflux of l‐serine. This profile mostly resembles system A members of the SLC38 family. In conclusion, the bidirectional transport of glutamine, glutamate, and aspartate by SLC38A10, and the immunostaining detected in neurons and astrocytes, suggest that SLC38A10 plays a role in pathways involved in neurotransmission.
Highlights
In brain cells, glutamine transporters are vital to monitor and control the levels of glutamate and GABA
The complete protein sequences were pairwise aligned between all SLC38 family members and the sequence identity between the members is presented in percent (%) (Fig. 2A)
For SLC38A10, the sequence identity is less than 10% with all other family members, and it does not fulfill the criteria (>20%) for being a SLC38 family member
Summary
Glutamine transporters are vital to monitor and control the levels of glutamate and GABA. There are 11 members of the SLC38 family of amino acid transporters of which eight have been functionally characterized. Using Xenopus laevis oocytes overexpressing SLC38A10, we show that SLC38A10 mediates bidirectional transport of Lglutamine, L-alanine, L-glutamate, and D-aspartate, and efflux of L-serine. This profile mostly resembles system A members of the SLC38 family. The bidirectional transport of glutamine, glutamate, and aspartate by SLC38A10, and the immunostaining detected in neurons and astrocytes, suggest that SLC38A10 plays a role in pathways involved in neurotransmission. Abbreviations EAAT, excitatory amino acid transporter; GGGC, glutamate/GABA-glutamine cycle; IHC, immunohistochemistry; mTORC1, mechanistic target of rapamycin complex 1; SLC, solute carrier; SNAT, sodium-coupled neutral amino acid transporter; TMHs, transmembrane helices
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