Title :

Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis

Author(s) :

Potelle, Sven [Auteur]
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Dulary, Eudoxie [Auteur]
Duvet, Sandrine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Vicogne, Dorothee [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Spriet, Corentin [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Krzewinski, Marie-Ange [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Morsomme, Pierre [Auteur]
Jaeken, Jaak [Auteur]
Matthijs, Gert [Auteur]
De Bettignies, Geoffroy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]

Journal title :

Human Molecular Genetics

Abbreviated title :

Hum. Mol. Genet.

Volume number :

25

Pages :

1489-1500

Publication date :

2016-04-15

ISSN :

1460-2083

English keyword(s) :

Golgi Apparatus
Congenital Disorders of Glycosylation
Humans
HEK293 Cells
Homeostasis
Fungal Proteins
Glycosylation
Membrane Protein
HeLa Cells
Mutation
Manganese
Vesicular Transport Proteins

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Congenital disorders of glycosylation (CDG) are severe inherited diseases in which aberrant protein glycosylation is a hallmark. From this genetically and clinically heterogenous group, a significant subgroup due to Golgi ...
Show more >Congenital disorders of glycosylation (CDG) are severe inherited diseases in which aberrant protein glycosylation is a hallmark. From this genetically and clinically heterogenous group, a significant subgroup due to Golgi homeostasis defects is emerging. We previously identified TMEM165 as a Golgi protein involved in CDG. Extremely conserved in the eukaryotic reign, the molecular mechanism by which TMEM165 deficiencies lead to Golgi glycosylation abnormalities is enigmatic. AsGDT1 is the ortholog of TMEM165 in yeast, both gdt1Δ null mutant yeasts and TMEM165 depleted cells were used. We highlighted that the observed Golgi glycosylation defects due to Gdt1p/TMEM165 deficiency result from Golgi manganese homeostasis defect. We discovered that in both yeasts and mammalian Gdt1p/TMEM165-deficient cells, Mn(2+) supplementation could restore a normal glycosylation. We also showed that the GPP130 Mn(2+) sensitivity was altered in TMEM165 depleted cells. This study not only provides novel insights into the molecular causes of glycosylation defects observed in TMEM165-deficient cells but also suggest that TMEM165 is a key determinant for the regulation of Golgi Mn(2+) homeostasis.Show less >

Language :

Anglais

Administrative institution(s) :

CNRS
Université de Lille

Collections :

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

Research team(s) :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Submission date :

2020-02-12T15:12:00Z