Ingele Casteels
Research Subjects
Research Interests
Ingele Casteels has a total of 33 co-authors. Here are the top co-authors by number of shared publications:
- Alberto Iannuzzo
Université Paris Cité, CNRS, Inserm, Institut Cochin, Paris, France
1 shared publication - Alice Lepelley
Université Paris Cité, Paris, France
1 shared publication - Anniek Corveleyn
Center for Human Genetics, Leuven University Hospitals, Leuven, Belgium
1 shared publication Arnout Voet
Laboratory of Biomolecular Modelling and Design, Department of Chemistry, KU Leuven, Leuven, Belgium
1 shared publication- Bram Boeckx
Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
1 shared publication - Bram Mylemans
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
1 shared publication
Latest Publications
- Open Access
- 19 December 2023
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 134 (4)
Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome
Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.
- 19 December 2023
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 134 (4)
Open AccessHeterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome
Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.