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

Autor: 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
Přispěvatelé: Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Department of Molecular Biology, Princeton University, HiLIFE - Institute of Biotechnology [Helsinki] (BI), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Faculty of Life Sciences [Manchester], University of Manchester [Manchester], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, University of Manchester Institute of Science and Technology [UMIST], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Chemistry [York, UK], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Department of Biology [York], Electron Microscopy, Institute of Biotechnology, Doctoral Programme in Integrative Life Science
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Glycosylation
119 Other natural sciences
Science
Golgi Apparatus
Dwarfism
Article
Coat Protein Complex I
ADP-RIBOSYLATION FACTOR
RECESSIVE FORM
OF-FUNCTION MUTATIONS
Humans
SCYL1
lcsh:Science
BETA-COP
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
COATED VESICLES
Bone Diseases
Carrier Proteins
Cells
Cultured
Enzymes
Golgi Matrix Proteins
HEK293 Cells
HeLa Cells
Mutation
Protein Binding
Protein Transport
RNA Interference
Skin Diseases
Genetic
Transcription Factors
COMPLEX
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
COATOMER
Skin Diseases
Genetic
GERODERMIA OSTEODYSPLASTICA
DNA-Binding Proteins
Adaptor Proteins
Vesicular Transport
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biomolecules [q-bio.BM]
MEMBRANE TRAFFICKING
lcsh:Q
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019)
Nature Communications
Nature Communications, Nature Publishing Group, 2019, 10 (1), ⟨10.1038/s41467-018-08044-6⟩
Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-018-08044-6⟩
ISSN: 2041-1723
DOI: 10.1038/s41467-018-08044-6⟩
Popis: 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.
COPI is recruited to the membrane by binding to Arf GTPases. Here the authors find that GORAB, a trans-Golgi protein, promotes COPI recruitment by forming membrane domains that also contain the COPI-interacting protein Scyl1, which is required for efficient glycosylation of cargo proteins.
Databáze: OpenAIRE
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