Impact of disease-causing mutations on ...
Document type :
Article dans une revue scientifique
DOI :
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Title :
Impact of disease-causing mutations on TMEM165 subcellular localization, a recently identified protein involved in CDG-II
Author(s) :
Rosnoblet, Claire [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Legrand, Dominique [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Demaegd, Didier [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Hacine-Gherbi, Hêla [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
De Bettignies, Geoffroy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bammens, Riet [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Borrego, Cindy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Duvet, Sandrine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Morsomme, Pierre [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Matthijs, Gert [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Legrand, Dominique [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Demaegd, Didier [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Hacine-Gherbi, Hêla [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
De Bettignies, Geoffroy [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bammens, Riet [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Borrego, Cindy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Duvet, Sandrine [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Morsomme, Pierre [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Matthijs, Gert [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Foulquier, Francois [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Journal title :
Human Molecular Genetics
Abbreviated title :
Hum. Mol. Genet.
Volume number :
22
Pages :
2914-2928
Publication date :
2013-07-15
ISSN :
1460-2083
English keyword(s) :
Cell Membrane
Golgi Apparatus
Point Mutation
Congenital Disorders of Glycosylation
Humans
Lysosomes
Membrane Protein
Protein Sorting Signals
Protein Transport
Endosomes
Golgi Apparatus
Point Mutation
Congenital Disorders of Glycosylation
Humans
Lysosomes
Membrane Protein
Protein Sorting Signals
Protein Transport
Endosomes
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
TMEM165 has recently been identified as a novel protein involved in CDG-II. TMEM165 has no biological function described so far. Different mutations were recently found in patients with Golgi glycosylation defects and ...
Show more >TMEM165 has recently been identified as a novel protein involved in CDG-II. TMEM165 has no biological function described so far. Different mutations were recently found in patients with Golgi glycosylation defects and harboring a peculiar skeletal phenotype. In this study, we examined the effect of naturally occurring mutations on the intracellular localization of TMEM165 and their abilities to complement the TMEM165-deficient yeast, gdt1▵. Wild-type TMEM165 was present within Golgi compartment, plasma membrane and late endosomes/lysosomes, whereas mutated TMEM165 were found differentially localized according to the mutations. We demonstrated that, in the yeast functional assay with TMEM165 ortholog Gdt1, the homozygous point mutation correlating with a mild phenotype restores the yeast functional assay, whereas the truncated mutation, associated with severe disease, failed to restore Gdt1 function. These studies highly suggest that these clinically relevant point mutations do not affect the protein function but critically changes the subcellular protein localization. Moreover, the data point to a critical role of the YNRL motif in TMEM165 subcellular localization.Show less >
Show more >TMEM165 has recently been identified as a novel protein involved in CDG-II. TMEM165 has no biological function described so far. Different mutations were recently found in patients with Golgi glycosylation defects and harboring a peculiar skeletal phenotype. In this study, we examined the effect of naturally occurring mutations on the intracellular localization of TMEM165 and their abilities to complement the TMEM165-deficient yeast, gdt1▵. Wild-type TMEM165 was present within Golgi compartment, plasma membrane and late endosomes/lysosomes, whereas mutated TMEM165 were found differentially localized according to the mutations. We demonstrated that, in the yeast functional assay with TMEM165 ortholog Gdt1, the homozygous point mutation correlating with a mild phenotype restores the yeast functional assay, whereas the truncated mutation, associated with severe disease, failed to restore Gdt1 function. These studies highly suggest that these clinically relevant point mutations do not affect the protein function but critically changes the subcellular protein localization. Moreover, the data point to a critical role of the YNRL motif in TMEM165 subcellular localization.Show less >
Language :
Anglais
Audience :
Non spécifiée
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Submission date :
2020-02-12T15:12:08Z
2021-03-04T15:11:24Z
2021-03-04T15:11:24Z