GORAB scaffolds COPI at the trans-Golgi ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation. Nature Communications
Author(s) :
Witkos, Tomasz M. [Auteur]
Chan, Wing Lee [Auteur]
Joensuu, Merja [Auteur]
Rhiel, Manuel [Auteur]
Pallister, Ed [Auteur]
Thomas-Oates, Jane [Auteur]
Mould, A. Paul [Auteur]
Mironov, Alex A. [Auteur]
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Ungar, Daniel [Auteur]
Wieland, Felix T. [Auteur]
Jokitalo, Eija [Auteur]
Tassabehji, May [Auteur]
Kornak, Uwe [Auteur]
Lowe, Martin [Auteur]
Chan, Wing Lee [Auteur]
Joensuu, Merja [Auteur]
Rhiel, Manuel [Auteur]
Pallister, Ed [Auteur]
Thomas-Oates, Jane [Auteur]
Mould, A. Paul [Auteur]
Mironov, Alex A. [Auteur]
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Ungar, Daniel [Auteur]
Wieland, Felix T. [Auteur]
Jokitalo, Eija [Auteur]
Tassabehji, May [Auteur]
Kornak, Uwe [Auteur]
Lowe, Martin [Auteur]
Journal title :
Nature Communications
Abbreviated title :
Nat Commun
Volume number :
10
Publisher :
Nature Publishing Group
Publication date :
2019-01-10
ISSN :
2041-1723
English keyword(s) :
Glycobiology
Golgi
Mechanisms of disease
Golgi
Mechanisms of disease
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates ...
Show more >COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.Show less >
Show more >COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Research team(s) :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Chemical Glycobiology
Chemical Glycobiology
Submission date :
2020-02-12T15:45:53Z
2020-12-07T13:59:11Z
2020-12-07T13:59:11Z
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