title: Distinct expression patterns of glycoprotein hormone-alpha2 and -beta5 in a basal chordate suggest independent developmental functions.
abstract: The vertebrate glycoprotein hormones (GpHs), gonadotropins and thyrotropin, are heterodimers composed of a common alpha- and specific beta-subunit. The recombinant heterodimer of two additional, structurally related proteins identified in vertebrate and protostome genomes, the glycoproteins-alpha2 (GPA2) and-beta5 (GPB5), was shown to activate the thyrotropin receptor and was therefore named thyrostimulin. However, differences in tissue distribution and expression levels of these proteins suggested that they might act as nonassociated factors, prompting further investigation on these proteins. In this study we show that GPA2 and GPB5 appeared with the emergence of bilateria and were maintained in most groups. These genes are tightly associated at the genomic level, an association, however, lost in tetrapods. Our structural and genomic environment comparison reinforces the hypothesis of their phylogenetic relationships with GpH-alpha and -beta. In contrast, the glycosylation status of GPA2 and GPB5 is highly variable further questioning heterodimer secretory efficiency and activity. As a first step toward understanding their function, we investigated the spatiotemporal expression of GPA2 and GPB5 genes at different developmental stages in a basal chordate, the amphioxus. Expression of GPB5 was essentially ubiquitous with an anteroposterior gradient in embryos. GPA2 embryonic and larvae expression was restricted to specific areas and, interestingly, partially overlapped that of a GpH receptor-related gene. In conclusion, we speculate that GPA2 and GPB5 have nondispensable and coordinated functions related to a novelty appeared with bilateria. These proteins would be active during embryonic development in a manner that does not require their heterodimerization.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 5166, Muséum National d'Histoire Naturelle Unité Scientifique du Muséum 501, Régulation, Développement et Diversité Moléculaire, F75231 Paris cedex 5, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dos Santos
authors.forename: Claire
authors.initials: C
authors.lastname: Bardet
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bertrand
authors.forename: Hector
authors.initials: H
authors.lastname: Escriva
authors.forename: Damien
authors.initials: D
authors.lastname: Habert
authors.forename: Bruno
authors.initials: B
authors.lastname: Querat
mesh_terms: D000818:Animals; D043344:Chordata / Q000145:classification / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D007814:Larva / Q000378:metabolism; D008957:Models, Genetic; D008958:Models, Molecular; D010802:Phylogeny; D055503:Protein Multimerization
chemical_list: D006023:Glycoproteins; C458339:thyrostimulin