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2 and -β5 in a Basal Chordate Suggest Independent Developmental FunctionsCentre National de la Recherche Scientifique Unité Mixte de Recherche 5166 (S.D.S., C.B., D.H., B.Q.), Muséum National d'Histoire Naturelle Unité Scientifique du Muséum 501, Régulation, Développement et Diversité Moléculaire, F75231 Paris cedex 5, France; and Centre National de la Recherche Scientifique Unité Mixte de Recherche 7628 (S.B., H.E.), Université Pierre et Marie Curie, Paris 06 Observatoire Océanographique, F-66651 Banyuls-sur-Mer, France
Address all correspondence and requests for reprints to: Bruno Querat, Universite Paris Diderot-Paris 7, Equipe d'Accueil Conventionnée 7059 Centre National de la Recherche Scientifique, Physiologie de lAxe Gonadotrope, Bâtiment Buffon, CC 7007, 5 Rue Thomas Mann, 75205 Paris cedex 13, France. E-mail: bruno.querat{at}univ-paris-diderot.fr.
The vertebrate glycoprotein hormones (GpHs), gonadotropins and thyrotropin, are heterodimers composed of a common
- and specific β-subunit. The recombinant heterodimer of two additional, structurally related proteins identified in vertebrate and protostome genomes, the glycoproteins-
2 (GPA2) and-β5 (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-
and -β. 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.
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V. L. Trudeau Really Old Hormones Up to New Tricks: Glycoprotein Hormone Subunits May Have Roles in Development Endocrinology, August 1, 2009; 150(8): 3446 - 3447. [Full Text] [PDF] |
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