The heterodimeric amino acid transporters (HAT) of the SLC7/SLC3 family: A structure-function relationships and relevance to human pathology

SLC transporters are the entry gates of nutrients required by intracellular enzymes to accomplish cell metabolism. SLCs include many amino acid transporters, which belong to different families and are characterized by redundancy, cross-specificity, and diverse transport mechanisms. Amino acid transporters are critical, as demonstrated by the onset of diseases caused by their altered expression, function, or localization. Despite their crucial roles, a systematic description of structure/function relationships of amino acid transporters is still far from being obtained. Among many SLCs specific toward amino acids, the heterodimeric transporters (HATs) of the SLC7 family, paired to proteins of the SLC3 family via a conserved disulfide, have emerged. Members A5 (LAT1), A6 (y+LAT2), A7 (y+LAT1), A8 (LAT2), A10 (ASC1), and A11 (xCT) are combined with SLC3A2; the members A9 (b0,+AT1) and A13 (AGT1) are combined with SLC3A1. Even though the members of the SLC3 family are classified as solute carriers (SLCs), they do not display transport capacity but are mainly involved in assisting the trafficking of the transport SLC7 subunits. An update of the structure/function relationships and relation to pathologies is reported.