Title :

GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation

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
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Ungar, Daniel [Auteur]
Wieland, Felix T. [Auteur]
Jokitalo, Eija [Auteur]
Tassabehji, May [Auteur]
Kornak, Uwe [Auteur]
Lowe, Martin [Auteur]

Journal title :

Nature communications

Volume number :

10

Pages :

127

Publication date :

2019-12

ISSN :

2041-1723

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 >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CNRS
Université de Lille

Collections :

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

Submission date :

2020-02-12T15:45:48Z
2024-02-23T12:00:31Z