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J Biol Chem. 2016 Aug 5;291(32):16553-66. doi: 10.1074/jbc.M116.719047. Epub 2016 Jun 16.

Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.

Author information

1
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
2
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan 48109.
3
Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, CNRS UMR 7221, Muséum National d'Histoire Naturelle, 7 rue Cuvier 75231 Paris cedex 05, France, and.
4
Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique, Université Claude Bernard Lyon 1, CNRS UMR 5086, Institut de Biologie et Chimie des Protéines, 7 passage du Vercors, 69367 Lyon cedex 07, France.
5
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan 48109, parvan@umich.edu.
6
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France, vincent.laudet@obs-banyuls.fr.

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 (Danio 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.

KEYWORDS:

Xenopus; metamorphosis; molecular evolution; thyroglobulin; thyroid; thyroid hormone; zebrafish

PMID:
27311711
PMCID:
PMC4974371
DOI:
10.1074/jbc.M116.719047
[Indexed for MEDLINE]
Free PMC Article

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