دورية أكاديمية
GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
| العنوان: | GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation |
|---|---|
| المؤلفون: | 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 |
| المساهمون: | Université de Lille, CNRS, University of Manchester Institute of Science and Technology UMIST, University of Helsinki, Universität Heidelberg Heidelberg, Department of Chemistry York, UK, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Department of Biology York |
| سنة النشر: | 2020 |
| المجموعة: | LillOA (Lille Open Archive - Université de Lille) |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. ; 10 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/rdf+xml; charset=utf-8; application/octet-stream |
| اللغة: | unknown |
| العلاقة: | Nature Communications; Nat Commun; http://hdl.handle.net/20.500.12210/33725.2Test |
| الإتاحة: | https://doi.org/20.500.12210/33725.2Test https://hdl.handle.net/20.500.12210/33725.2Test |
| حقوق: | Attribution 3.0 United States ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.120F94F4 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |