Abnormal cartilage development and altered ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Abnormal cartilage development and altered N-glycosylation in Tmem165-deficient zebrafish mirrors the phenotypes associated with TMEM165-CDG
Auteur(s) :
Bammens, Riet [Auteur]
Mehta, Nickita [Auteur]
Race, Valérie [Auteur]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Jaeken, Jaak [Auteur]
Tiemeyer, Michael [Auteur]
Steet, Richard [Auteur]
Matthijs, Gert [Auteur]
Flanagan-Steet, Heather [Auteur]
Mehta, Nickita [Auteur]
Race, Valérie [Auteur]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Jaeken, Jaak [Auteur]
Tiemeyer, Michael [Auteur]
Steet, Richard [Auteur]
Matthijs, Gert [Auteur]
Flanagan-Steet, Heather [Auteur]
Titre de la revue :
Glycobiology
Nom court de la revue :
Glycobiology
Numéro :
25
Pagination :
669-682
Date de publication :
2015-06
ISSN :
1460-2423
Mot(s)-clé(s) en anglais :
Cartilage
Phenotype
Animals
Congenital Disorders of Glycosylation
Humans
Zebrafish
Glycosylation
Membrane Protein
N-Glycosylation
Disease Models, Animal
Phenotype
Animals
Congenital Disorders of Glycosylation
Humans
Zebrafish
Glycosylation
Membrane Protein
N-Glycosylation
Disease Models, Animal
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
The congenital disorders of glycosylation (CDG), a group of inherited diseases characterized by aberrant glycosylation, encompass a wide range of defects, including glycosyltransferases, glycosidases, nucleotide-sugar ...
Lire la suite >The congenital disorders of glycosylation (CDG), a group of inherited diseases characterized by aberrant glycosylation, encompass a wide range of defects, including glycosyltransferases, glycosidases, nucleotide-sugar transporters as well as proteins involved in maintaining Golgi architecture, pH and vesicular trafficking. Mutations in a previously undescribed protein, TMEM165, were recently shown to cause a new form of CDG, termed TMEM165-CDG. TMEM165-CDG patients exhibit cartilage and bone dysplasia and altered glycosylation of serum glycoproteins. We utilized a morpholino knockdown strategy in zebrafish to investigate the physiologic and pathogenic functions of TMEM165. Inhibition of tmem165 expression in developing zebrafish embryos caused craniofacial abnormalities, largely attributable to fewer chondrocytes. Decreased expression of several markers of cartilage and bone development suggests that Tmem165 deficiency alters both chondrocyte and osteoblast differentiation. Glycomic analysis of tmem165 morphants also revealed altered initiation, processing and extension of N-glycans, paralleling some of the glycosylation changes noted in human patients. Collectively, these findings highlight the utility of zebrafish to elucidate pathogenic mechanisms associated with glycosylation disorders and suggest that the cartilage and bone dysplasia manifested in TMEM165-CDG patients may stem from abnormal development of chondrocytes and osteoblasts.Lire moins >
Lire la suite >The congenital disorders of glycosylation (CDG), a group of inherited diseases characterized by aberrant glycosylation, encompass a wide range of defects, including glycosyltransferases, glycosidases, nucleotide-sugar transporters as well as proteins involved in maintaining Golgi architecture, pH and vesicular trafficking. Mutations in a previously undescribed protein, TMEM165, were recently shown to cause a new form of CDG, termed TMEM165-CDG. TMEM165-CDG patients exhibit cartilage and bone dysplasia and altered glycosylation of serum glycoproteins. We utilized a morpholino knockdown strategy in zebrafish to investigate the physiologic and pathogenic functions of TMEM165. Inhibition of tmem165 expression in developing zebrafish embryos caused craniofacial abnormalities, largely attributable to fewer chondrocytes. Decreased expression of several markers of cartilage and bone development suggests that Tmem165 deficiency alters both chondrocyte and osteoblast differentiation. Glycomic analysis of tmem165 morphants also revealed altered initiation, processing and extension of N-glycans, paralleling some of the glycosylation changes noted in human patients. Collectively, these findings highlight the utility of zebrafish to elucidate pathogenic mechanisms associated with glycosylation disorders and suggest that the cartilage and bone dysplasia manifested in TMEM165-CDG patients may stem from abnormal development of chondrocytes and osteoblasts.Lire moins >
Langue :
Anglais
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Date de dépôt :
2020-02-12T15:12:04Z