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GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
Copyright policy )UKRI| Dissecting the function of GORAB, the protein mutated in Geroderma osteodysplastica ,
WT| The Dynamics of Cellular Pathways
Christophe Biot; Yann Guérardel; Felix T. Wieland; Merja Joensuu; Merja Joensuu; Merja Joensuu; May Tassabehji; +15 Authors
Christophe Biot; Yann Guérardel; Felix T. Wieland; Merja Joensuu; Merja Joensuu; Merja Joensuu; May Tassabehji; May Tassabehji; Uwe Kornak; Uwe Kornak; Wing Lee Chan; Wing Lee Chan; Tomasz M. Witkos; Jane Thomas-Oates; Alex A. Mironov; Daniel Ungar; Martin Lowe; A. Paul Mould; Manuel Rhiel; Eija Jokitalo; Willy Morelle; Ed Pallister;
GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
AbstractCOPI 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.
- French National Centre for Scientific Research France
- Manchester University NHS Foundation Trust United Kingdom
- University of Lille France
- Freie Universität Berlin Germany
- Unité de Glycobiologie Structurale et Fonctionnelle France
Beta-Cop, 1300, Glycosylation, Coatomer, Golgi Apparatus, Gerodermia Osteodysplastica, Coat Protein Complex I, OF-FUNCTION MUTATIONS, 3100 Physics and Astronomy, SCYL1, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], BETA-COP, Cells, Cultured, COATED VESICLES, Q, Skin Diseases, Genetic, 1600 Chemistry, Enzymes, DNA-Binding Proteins, Protein Transport, MEMBRANE TRAFFICKING, Of-Function Mutations, RNA Interference, Bone Diseases, Protein Binding, Adp-Ribosylation Factor, 1300 Biochemistry, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, Coated Vesicles, 1600, Genetics and Molecular Biology, Dwarfism, Scyl1, 3100, Article, ADP-RIBOSYLATION FACTOR, Complex, RECESSIVE FORM, Humans, 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, COMPLEX, Recessive Form, COATOMER, Golgi Matrix Proteins, GERODERMIA OSTEODYSPLASTICA, Other natural sciences, Adaptor Proteins, Vesicular Transport, HEK293 Cells, Membrane Trafficking, Mutation, Carrier Proteins, HeLa Cells, Transcription Factors
Beta-Cop, 1300, Glycosylation, Coatomer, Golgi Apparatus, Gerodermia Osteodysplastica, Coat Protein Complex I, OF-FUNCTION MUTATIONS, 3100 Physics and Astronomy, SCYL1, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], BETA-COP, Cells, Cultured, COATED VESICLES, Q, Skin Diseases, Genetic, 1600 Chemistry, Enzymes, DNA-Binding Proteins, Protein Transport, MEMBRANE TRAFFICKING, Of-Function Mutations, RNA Interference, Bone Diseases, Protein Binding, Adp-Ribosylation Factor, 1300 Biochemistry, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, Coated Vesicles, 1600, Genetics and Molecular Biology, Dwarfism, Scyl1, 3100, Article, ADP-RIBOSYLATION FACTOR, Complex, RECESSIVE FORM, Humans, 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, COMPLEX, Recessive Form, COATOMER, Golgi Matrix Proteins, GERODERMIA OSTEODYSPLASTICA, Other natural sciences, Adaptor Proteins, Vesicular Transport, HEK293 Cells, Membrane Trafficking, Mutation, Carrier Proteins, HeLa Cells, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).43 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 67 downloads 42 - 67views42downloads
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
Popularity provided by BIP!influenceInfluence provided by BIP!
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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