Visualising trafficking of trace amine-associated receptors (TAAR) in polarised thyroid epithelial cells

Trace amine-associated receptors (Taar) are seven-transmembrane G protein-coupled receptors (GPCR) that bind a wide range of trace amine agonists, including TH derivatives, thyronamines, as potent activators. We hypothesise that Taar1 is expressed by thyroid epithelial cells where it performs a modulatory function of thyroid homeostasis, possibly by signalling in a negative feedback loop upon thyronamine activation, which would contribute to thyroid auto-regulation. Thus, visualising transport pathways of Taar is important to better understand the potential physiological implications of these GPCRs.

Thyroid epithelial cell lines were used as in vitro models to express chimeric mouse Taar1, Taar5 and Taar8b, either N-terminally or C-terminally fused to haemagglutinin (HA) or enhanced green fluorescent protein (eGFP) tags, respectively. Our data show Taar chimeras to be localised in various compartments along the secretory route, including the endoplasmic reticulum and the Golgi apparatus. The same data also suggests that Taar heterodimerisation promotes or enhances trafficking to the cell surface, while the cells maintained their polarisation states and revealed no signs of unfolded protein response. Taar chimeras were abundant along the secretory route, and reached the cell surface of epithelial cells.

We conclude that it is possible to express Taar's in heterologous cellular systems without interfering with the transport of endogenous cellular proteins or the physiological states of the cells. In principle, such expression systems are suited to be used in future for signalling studies.

Supported by Deutsche Forschungsgemeinschaft, SPP 1629, BR1308/11 – 1.