The Solute Carrier Family 1A (SLC1A) includes membrane bound transporters for acidic and neutral amino acids¹. Members of this family are responsible for regulating amino acids pools in the body and strictly controlling excitatory neurotransmitter concentrations in the brain. Despite the high degree of amino acid sequence identity between family members, the ASCTs (Alanine, Serine, Cysteine Transporters) function as electroneutral exchangers while the human Excitatory Amino Acid Transporters (EAATs) and the archaeal transporter (Glt_Ph) actively transport acidic amino acids.
We have used site-directed mutagenesis in combination with functional analysis and X-ray crystallography to identify the molecular basis for the differences in substrate selectivity in both human and prokaryotic members of the SLC1A family. This information is being used to develop sub-type selective compounds that may be used to treat a variety of diseases including cancer. Cancer cells upregulate amino acid transporters to increase their ability to obtain nutrients to fuel their increased growth and proliferation. ASCT2 is known to be upregulated in certain cancers including melanoma, where inhibition of ASCT2 suppresses cancer cell growth².

¹Vandenberg RJ and Ryan RM (2013) Mechanisms of Glutamate Transport. Physiological Reviews 93(4):1621-57
²Qian Wang, Kimberley A. Beaumont, Nicholas J. Otte, Josep Font, Charles G. Bailey, Michelle van Geldermalsen, Danae Sharp, Jessamy C. Tiffen, Renae M Ryan, Mika Jormakka, Nikolas K. Haass, John E. J. Rasko, Jeff Holst (2014) Targeting glutamine transport to suppress melanoma cell growth. International Journal of Cancer 135(5):1060-71