ZFIN ID: ZDB-PUB-180908-10
Functional characterization of thyrostimulin in amphioxus suggests an ancestral origin of the TH signaling pathway
Wang, P., Liu, S., Yang, Q., Liu, Z., Zhang, S.
Date: 2018
Source: Endocrinology   159(10): 3536-3548 (Journal)
Registered Authors: Liu, Zhenhui
Keywords: none
MeSH Terms:
  • Animals
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Gene Expression Profiling
  • Glycoproteins/classification
  • Glycoproteins/genetics
  • Glycoproteins/metabolism*
  • Lancelets/genetics
  • Lancelets/metabolism*
  • Phylogeny
  • Protein Binding
  • Protein Kinase C/metabolism
  • Receptors, Thyrotropin/genetics
  • Receptors, Thyrotropin/metabolism
  • Sequence Analysis, DNA
  • Signal Transduction*
  • Thyroid Hormones/metabolism*
PubMed: 30192937 Full text @ Endocrinology
Thyrostimulin, consisting of GpA2 and GpB5 subunits, has been identified in amphioxus, but to date, little is known about the roles of GPA2/GPB5-type hormone in this evolutionarily important animal. We showed here that amphioxus GpA2, GpB5 and TSHR represented the archetypes of vertebrate TSHα, TSHβ and TSHR, respectively, and both gpa2 and gpb5 were co-expressed in the Hatschek's pit, a homologue of the vertebrate pituitary, in amphioxus. We also showed that recombinant amphioxus GpA2 and GpB5, like zebrafish TSHα and TSHβ, bound to both amphioxus and zebrafish TSHR, and that tethered amphioxus thyrostimulin activated both protein kinase A and protein kinase C pathways in the cells expressing amphioxus TSHR. Moreover, we demonstrated that recombinant amphioxus thyrostimulin induced the production of thyroid hormone T4. Because genuine TSH is absent in amphioxus and thyrostimulin is the only and sole glycoprotein hormone, our data in all possibility provide evidence that amphioxus thyrostimulin is a functional glycoprotein hormone which plays a role as TSH does in the vertebrates. The data also suggest that the TH signaling pathway had evolved in the basal chordate more than 500 million years ago.