Endocrine Abstracts

Thyroid hormones (THs) are transported into their target cells by diverse transmembrane transporter proteins, e.g. by members of the L-type amino acid transporter (LAT) family. The Lat2 is a sodium independent amino acid exchanger and interacts with CD98 for its efficient cell surface expression. So far the role of Lat2 in TH transport including the transport mechanisms is unclear. It is important to determine TH subtype specificity and to identify amino acids at Lat2 which are involved in the substrate recognition and transport.

By using Xenopus laevis oocytes as expression system we could demonstrate a noticeable increase in 3,3′-T2 and to some extent also in T3 uptake by Lat2. We are able to induce the specific 3,3′-T2 uptake by Lat2 coexpressed with CD98. The 3,3′-T2 uptake is sodium independent and the calculated KM value is in a low micromolar range. To gain insight into properties of THs transported by Lat2 we used TH derivatives differing in their number of iodine atoms and could show a strong competition on 3,3′-T2 uptake by THs like 3-T1 and other T2 derivatives.

In addition, the transport mechanisms by Lat2 are unknown and neither a molecular structure nor a homology model is available. Therefore, we generated the first molecular homology model of Lat2, which is based on two X-ray structures, arginine/agmantine antiporter (AdiC) and amino acid polyamine and organocation transporter (ApcT). We verified our model with published functional features and in vitro transport studies of Lat2 mutants.

In conclusion, our results demonstrate that Lat2 is involved in 3,3′-T2 transport and might contribute to termination of TH action. Furthermore, for a better understanding of transport mechanisms for TH influx and efflux in cells we will use our molecular model to identify TH recognition patterns.