PUBLICATION
Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates
- Authors
- Holzer, G., Morishita, Y., Fini, J.B., Lorin, T., Gillet, B., Hughes, S., Tohmé, M., Deléage, G., Demeneix, B., Arvan, P., Laudet, V.
- ID
- ZDB-PUB-160618-24
- Date
- 2016
- Source
- The Journal of biological chemistry 291(32): 16553-66 (Journal)
- Registered Authors
- Laudet, Vincent
- Keywords
- Xenopus, metamorphosis, molecular evolution, thyroglobulin, thyroid, thyroid hormone, zebrafish
- MeSH Terms
-
- Animals
- Evolution, Molecular*
- Lampreys/genetics*
- Rats
- Thyroglobulin/genetics*
- Xenopus
- Xenopus Proteins/genetics*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- PubMed
- 27311711 Full text @ J. Biol. Chem.
Citation
Holzer, G., Morishita, Y., Fini, J.B., Lorin, T., Gillet, B., Hughes, S., Tohmé, M., Deléage, G., Demeneix, B., Arvan, P., Laudet, V. (2016) Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates. The Journal of biological chemistry. 291(32):16553-66.
Abstract
Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology and behavior), but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study, we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Dano rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function are well conserved, despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs, and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter. after.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping