The Quantitative Expression of Transport Proteins SLC38A1-11 in Nerve Cell Development

Sammanfattning: Solute carriers consist of over 400 genes and 66 subfamilies and are the largest group of membrane bound transporters. They facilitate movement of many molecules through cells and organelles and are crucial for upholding many key functions in the human body. They are also involved in the pathophysiology of several diseases. The sodium-coupled neutral amino acid transporter family (SLC38) consists of 11 known transporters classified into system A and system N. They are responsible for influx and efflux of amino acids in different tissues, and the broad majority are expressed in various brain regions. The transporters are involved in gamma-aminobutyric acid (GABA)/glutamine metabolism, liver metabolism, the mammalian target of rapamycin pathway, among many other pathways and mechanisms. This study quantitatively investigates the mRNA expression of the transporters in human nerve cells from differentiation day 0 to 30, with the main focus being on the Golgi/ER localized SLC38A10. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to run quantitative assays on nerve cells from day 0, 5, 10, 15 and 30 in nerve cell differentiation, with histone variant H3.3 and Ribosomal Protein L13a as housekeeping genes. It was found that the genes SLC38A1, A2, A3, A8 and A10 had relatively similar expression patterns in the nerve cell tissues tested. No expression was detected for SLC38A5, A6, A9 and A11. SLC38A4 had no clear expression pattern in the nerve cell tissues, although expression was detected in some assays, which was not expected in nerve cells. SLC38A10 demonstrated the highest expression, and lowest expression levels were seen for SLC38A4. SLC38A1, A2, A3, A8 and A10 had highest expression in day 0 nerve cells. These results indicate that precursor neurons could be most suitable to use for knockout studies of SLC38A10, as well as for SLC38A1, A2, A3 and A8, as these cells demonstrated the highest levels of expression of these genes. Further studies are encouraged into the expression levels of the SLC38 transporters, their roles in the human body and disease pathophysiology, and, ultimately, their potential as drug targets.