Titre :

Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects

Auteur(s) :

Rujano, Maria A. [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Cannata Serio, Magda [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Panasyuk, Ganna [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Péanne, Romain [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Reunert, Janine [Auteur]
University Hospital Münster - Universitaetsklinikum Muenster [Germany] [UKM]
Rymen, Daisy [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Hauser, Virginie [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Park, Julien H. [Auteur]
University Hospital Münster - Universitaetsklinikum Muenster [Germany] [UKM]
Freisinger, Peter [Auteur]
Reutlingen University
Souche, Erika [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Guida, Maria Clara [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Maier, Esther M. [Auteur]
Wada, Yoshinao [Auteur]
Jäger, Stefanie [Auteur]
University of California [San Francisco] [UC San Francisco]
Krogan, Nevan J. [Auteur]
University of California [San Francisco] [UC San Francisco]
Kretz, Oliver [Auteur]
Centre for Biological Signaling Studies [Freiburg] [BIOSS]
Nobre, Susana [Auteur]
Hospitais da Universidade de Coimbra [H.U.C.]
Garcia, Paula [Auteur]
Hospitais da Universidade de Coimbra [H.U.C.]
Quelhas, Dulce [Auteur]
Faculdade de Medicina da Universidade do Porto [FMUP]
Bird, Thomas D. [Auteur]
University of Washington [Seattle]
Raskind, Wendy H. [Auteur]
University of Washington [Seattle]
Schwake, Michael [Auteur]
Universität Bielefeld = Bielefeld University
Duvet, Sandrine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Matthijs, Gert [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Marquardt, Thorsten [Auteur]
University Hospital Münster - Universitaetsklinikum Muenster [Germany] [UKM]
Simons, Matias [Auteur]
Université Paris Descartes - Paris 5 [UPD5]

Titre de la revue :

The Journal of Experimental Medicine

Nom court de la revue :

J. Exp. Med.

Numéro :

214

Pagination :

3707-3729

Date de publication :

2017-12-04

ISSN :

1540-9538

Mot(s)-clé(s) en anglais :

Endoplasmic Reticulum-Associated Degradation
Brain
Humans
Liver
Cutis Laxa
Male
Lipids
Infant
Receptors, Cell Surface
Autophagy
Young Adult
Genes, X-Linked
Base Sequence
Fibroblasts
Vacuolar Proton-Translocating ATPases
Amino Acid Sequence
Drosophila Proteins
Glycosylation
Neural Stem Cells
Animals
Blood Proteins
Proton-Translocating ATPases
Adolescent
Protein Binding
Mice
Membrane Protein
Protein Processing, Post-Translational
Mutation
Liver Diseases
Drosophila melanogaster
Psychomotor Disorders

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify ...
Lire la suite >The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Projet Européen :

ERA-NET rare disease research implementing IRDiRC objectives

Projet ANR :

Institut Hospitalo-Universitaire Imagine
Utilisation de Drosophila melanogaster pour étudier les maladies génétiques du rein
Déterminants moléculaires de l'homéostasie hépatique nutritive

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Date de dépôt :

2020-02-12T15:11:55Z
2021-06-29T11:45:42Z