Rat Dio2 Stable Cell Line - HEK293

Thyroid gland damage brought on by an autoimmune disease or surgical excision causes hypothyroidism. The biological mechanisms behind the Thr92Ala polymorphism in the D2 gene (DIO2), which affects levothyroxine (LT4) medication, were examined by the researchers using cell lines. They examined the location and functionality of proteins using cell lines that expressed both wild-type and Ala92-D2 variations. They found that D2 is a cargo protein that recycles between the ER and Golgi in the ER Golgi Intermediary Compartment (ERGIC) vesicles. Reduced T3 synthesis resulted from the unfolded protein response (UPR) and ER stress caused by the Thr92-to-Ala change. After receiving treatment with the pharmacological chaperone 4-phenyl butyric acid (4-PBA), T3 levels were raised and ER stress was reduced. These results emphasize the role that cellular proteo-stasis plays in the control of thyroid hormone.

Figure 1. The Thr92Ala-DIO2 effect was investigated by the researchers using HEK-293 cells that were stable in producing His- and YFP-tagged D2. Immunofluorescence with specific antibodies revealed D2 recycling between the Golgi apparatus and ER. (Jo S, et al., 2019)