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

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http://hdl.handle.net/10138/311949

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Witkos , T M , Chan , W L , Joensuu , M , Rhiel , M , Pallister , E , Thomas-Oates , J , Mould , A P , Mironov , A A , Biot , C , Guerardel , Y , Morelle , W , Ungar , D , Wieland , F T , Jokitalo , E , Tassabehji , M , Kornak , U & Lowe , M 2019 , ' GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation ' , Nature Communications , vol. 10 , 127 . https://doi.org/10.1038/s41467-018-08044-6

Title: GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
Author: Witkos, Tomasz M.; Chan, Wing Lee; Joensuu, Merja; Rhiel, Manuel; Pallister, Ed; Thomas-Oates, Jane; Mould, A. Paul; Mironov, Alex A.; Biot, Christophe; Guerardel, Yann; Morelle, Willy; Ungar, Daniel; Wieland, Felix T.; Jokitalo, Eija; Tassabehji, May; Kornak, Uwe; Lowe, Martin
Contributor: University of Helsinki, University of Queensland
University of Helsinki, Electron Microscopy
Date: 2019-01-10
Language: eng
Number of pages: 18
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/311949
Abstract: 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.
Subject: ADP-RIBOSYLATION FACTOR
OF-FUNCTION MUTATIONS
BETA-COP
COATED VESICLES
GERODERMIA OSTEODYSPLASTICA
MEMBRANE TRAFFICKING
RECESSIVE FORM
COATOMER
COMPLEX
SCYL1
119 Other natural sciences
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