Molecular features of the L-type amino acid transporter 2 determine different import and export profiles for thyroid hormones and amino acids.

The L-type amino acid transporter 2 (LAT2) imports amino acids (AA) and also certain thyroid hormones (TH), e.g. 3,3'-T and T, but not rT and T. We utilized LAT2 mutations (Y130A, N133S, F242W) that increase 3,3'-T import and focus here on import and export capacity for AA, T, T, BCH and derivatives thereof to delineate molecular features. Transport studies and analysis of competitive inhibition of import by radiolabelled TH and AA were performed in Xenopus laevis oocytes. Only Y130A, a pocket widening mutation, enabled import for T and increased it for T. Mutant F242W showed increased 3,3'-T import but no import rates for other TH derivatives. No export was detected for any TH by LAT2-wild type (WT). Mutations Y130A and N133S enabled only the export of 3,3'-T, while N133S also increased AA export. Thus, distinct molecular LAT2-features determine bidirectional AA transport but only an unidirectional 3,3'-T and T import.