Witkos, Tomasz M., Chan, Wing Lee, Joensuu, Merja et al. (14 more authors) (2019) GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation. Nature Communications. 127. ISSN 2041-1723
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 major disease mechanism in gerodermia osteodysplastica.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Bone Diseases/congenital,Carrier Proteins/genetics,Cells, Cultured,Coat Protein Complex I/genetics,Dwarfism/genetics,Enzymes/metabolism,Glycosylation,Golgi Apparatus/metabolism,HEK293 Cells,HeLa Cells,Humans,Mutation,Protein Binding,Protein Transport,RNA Interference,Skin Diseases, Genetic/genetics,Transcription Factors/genetics |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 11 Dec 2018 14:40 |
Last Modified: | 16 Oct 2024 15:19 |
Published Version: | https://doi.org/10.1038/s41467-018-08044-6 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-018-08044-6 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:139718 |
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