Title :

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

Author(s) :

Witkos, Tomasz M [Auteur]
University of Manchester Institute of Science and Technology [UMIST]
Chan, Wing Lee [Auteur]
Joensuu, Merja [Auteur]
Helsingin yliopisto = Helsingfors universitet = University of Helsinki
Rhiel, Manuel [Auteur]
Universität Heidelberg [Heidelberg] = Heidelberg University
Pallister, Ed [Auteur]
Department of Chemistry [York, UK]
Thomas-Oates, Jane [Auteur]
Department of Chemistry [York, UK]
Mould, A Paul [Auteur]
University of Manchester Institute of Science and Technology [UMIST]
Mironov, Alex A [Auteur]
University of Manchester Institute of Science and Technology [UMIST]
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Ungar, Daniel [Auteur]
Department of Biology [York]
Wieland, Felix T [Auteur]
Universität Heidelberg [Heidelberg] = Heidelberg University
Jokitalo, Eija [Auteur]
Helsingin yliopisto = Helsingfors universitet = University of Helsinki
Tassabehji, May [Auteur]
University of Manchester Institute of Science and Technology [UMIST]
Kornak, Uwe [Auteur]
Lowe, Martin [Auteur]
University of Manchester Institute of Science and Technology [UMIST]

Journal title :

Nature Communications

Abbreviated title :

Nat Commun

Volume number :

10

Pages :

127

Publication date :

2019-01-10

ISSN :

2041-1723

English keyword(s) :

Bone Diseases
Carrier Proteins
Cells
Cultured
Coat Protein Complex I
Dwarfism
Enzymes
Glycosylation
Golgi Apparatus
Golgi Matrix Proteins
HEK293 Cells
HeLa Cells
Humans
Mutation
Protein Binding
Protein Transport
RNA Interference
Skin Diseases
Genetic
Transcription Factors

HAL domain(s) :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]

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 >

Audience :

Non spécifiée

Administrative institution(s) :

Université de Lille
CNRS

Collections :

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

Submission date :

2020-11-18T14:02:08Z
2020-11-25T07:02:42Z