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Editorial
. 2019 Jan 30:10:19.
doi: 10.3389/fendo.2019.00019. eCollection 2019.

Editorial: TSH Receptor and Autoimmunity

Terry F Davies  1 , Rauf Latif  1
Affiliations
Editorial

Editorial: TSH Receptor and Autoimmunity

Terry F Davies et al. Front Endocrinol (Lausanne). .
No abstract available

Keywords: GPCR (G-protein-coupled receptors); TSH (thyroid stimulating hormone); TSHR (thyroid-stimulating hormone receptor); autoantibodies; small molecule.

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Figures

Figure 1
Figure 1
Homology model of the entire TSH holoreceptor. This model highlights the tripartite structure of the TSHR. The ectodomain, shown in gray/black, is made up of 10 leucine-rich repeat domains (LRD) characterized as a “scythe-blade” shaped structure with loops and β pleated sheets obtained from the published crystal structure (1) (PDB:3G04). The region connecting the LRD and transmembrane domain (TMD), known as the “hinge” region, has recently been crystallized for the FSH receptor (2) (PDB:4AY9) and is shown as a looped structure (orange) with a helix conformation close to the carboxyl end of the LRD. The hinge in the TSHR has an additional sequence insert and is larger than in the FSH receptor. Therefore, amino acids 305-381 are missing in the illustrated model (3) and this insert is depicted as a closed dotted loop. The TMD (yellow), with its seven helices, is depicted as cylindrical structures connected to each other by the specific TSHR intra and extracellular loops. The TMD is the region that harbors the allosteric binding pockets for the SMLs. LRD, leucine-rich domain; TMD, transmembrane domain; ECL, extracellular loops; and ICL, intracellular loops [Figure adapted from (4)].
Figure 2
Figure 2
Generic life-cycle of the TSH receptor. The TSHR residing on the plasma membrane of thyrocytes on binding with its cognate ligand, TSH, is activated and in turn undergoes conformational changes to recruit and activate a G protein complex leading to a predominate wave of Gs generated cAMP (Signal 1). The activated receptor, after signal 1, is phosphorylated and then moved to clathrin-coated pits where β-arrestin is bound to the activated receptor. At this stage it is believed that the receptor can signal via arrestin leading to β-arrestin-associated signals. Furthermore, this activated receptor in the invaginated pits is pinched-off to form the early and late endosomes. It is described that within the endosome the receptor with its associated ligand and second messengers is capable of giving out a second wave cAMP signal (Signal 2). Following this the receptor can be either degraded or it enters recycling vesicles and is recycled to the plasma membrane whereas the ligand is transported to the lysosome and is degraded. This is the life that the TSHR lives on the surface of thyrocytes or any other cell where it is expressed.
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  • Editorial on the Research Topic TSH Receptor and Autoimmunity

References

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