Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism.

Détails

ID Serval
serval:BIB_19FB89539771
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Tornberg J., Sykiotis G.P., Keefe K., Plummer L., Hoang X., Hall J.E., Quinton R., Seminara S.B., Hughes V., Van Vliet G., Van Uum S., Crowley W.F., Habuchi H., Kimata K., Pitteloud N., Bülow H.E.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2011
Volume
108
Numéro
28
Pages
11524-11529
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Neuronal development is the result of a multitude of neural migrations, which require extensive cell-cell communication. These processes are modulated by extracellular matrix components, such as heparan sulfate (HS) polysaccharides. HS is molecularly complex as a result of nonrandom modifications of the sugar moieties, including sulfations in specific positions. We report here mutations in HS 6-O-sulfotransferase 1 (HS6ST1) in families with idiopathic hypogonadotropic hypogonadism (IHH). IHH manifests as incomplete or absent puberty and infertility as a result of defects in gonadotropin-releasing hormone neuron development or function. IHH-associated HS6ST1 mutations display reduced activity in vitro and in vivo, suggesting that HS6ST1 and the complex modifications of extracellular sugars are critical for normal development in humans. Genetic experiments in Caenorhabditis elegans reveal that HS cell-specifically regulates neural branching in vivo in concert with other IHH-associated genes, including kal-1, the FGF receptor, and FGF. These findings are consistent with a model in which KAL1 can act as a modulatory coligand with FGF to activate the FGF receptor in an HS-dependent manner.
Mots-clé
Adult, Amino Acid Sequence, Amino Acid Substitution, Animals, Caenorhabditis elegans/genetics, Caenorhabditis elegans/metabolism, Caenorhabditis elegans Proteins/genetics, Caenorhabditis elegans Proteins/metabolism, Child, Extracellular Matrix Proteins/genetics, Extracellular Matrix Proteins/metabolism, Female, Genes, Helminth, Humans, Hypogonadism/enzymology, Hypogonadism/genetics, Intercellular Signaling Peptides and Proteins/genetics, Intercellular Signaling Peptides and Proteins/metabolism, Kallmann Syndrome/enzymology, Kallmann Syndrome/genetics, Male, Middle Aged, Models, Molecular, Molecular Sequence Data, Mutation, Mutation, Missense, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Pedigree, Receptor, Fibroblast Growth Factor, Type 1/genetics, Receptor, Fibroblast Growth Factor, Type 1/metabolism, Receptors, Fibroblast Growth Factor/genetics, Receptors, Fibroblast Growth Factor/metabolism, Sequence Homology, Amino Acid, Species Specificity, Sulfotransferases/chemistry, Sulfotransferases/deficiency
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/02/2012 11:34
Dernière modification de la notice
20/08/2019 13:51
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