Language:

Deficiency in coatomer complex I causes aberrant activation of STING signalling

Nature communications, 2022-04, Vol.13 (1), p.2321-2321, Article 2321 [Peer Reviewed Journal]

2022. The Author(s). ;The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2022 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-022-29946-6 ;PMID: 35484149

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Deficiency in coatomer complex I causes aberrant activation of STING signalling
Author: Steiner, Annemarie ; Hrovat-Schaale, Katja ; Prigione, Ignazia ; Yu, Chien-Hsiung ; Laohamonthonkul, Pawat ; Harapas, Cassandra R ; Low, Ronnie Ren Jie ; De Nardo, Dominic ; Dagley, Laura F ; Mlodzianoski, Michael J ; Rogers, Kelly L ; Zillinger, Thomas ; Hartmann, Gunther ; Gantier, Michael P ; Gattorno, Marco ; Geyer, Matthias ; Volpi, Stefano ; Davidson, Sophia ; Masters, Seth L
Subjects: Cell lines ; Chronic obstructive pulmonary disease ; Coat Protein Complex I - metabolism ; COP-Coated Vesicles - metabolism ; Deoxyribonucleic acid ; DNA ; Electron Transport Complex I - metabolism ; Endoplasmic reticulum ; Golgi apparatus ; Humans ; Immunosensors ; Inflammatory diseases ; Interferon ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Mutation ; Nucleotidyltransferases - genetics ; Nucleotidyltransferases - metabolism ; Peripheral blood mononuclear cells ; Signal Transduction ; Signaling
Is Part Of: Nature communications, 2022-04, Vol.13 (1), p.2321-2321, Article 2321
Description: Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unknown. Using in vitro models we find aberrant activation of the STING pathway due to deficient retrograde but probably not intra-Golgi transport. Further we find the upstream cytosolic DNA sensor cGAS as essentially required to drive type I IFN signalling. Genetic deletion of COPI subunits COPG1 or COPD similarly induces type I IFN activation in vitro, which suggests that inflammatory diseases associated with mutations in other COPI subunit genes may exist. Finally, we demonstrate that inflammation in COPA syndrome patient peripheral blood mononuclear cells and COPI-deficient cell lines is ameliorated by treatment with the small molecule STING inhibitor H-151, suggesting targeted inhibition of the cGAS/STING pathway as a promising therapeutic approach.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-022-29946-6
PMID: 35484149
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Deficiency in coatomer complex I causes aberrant activation of STING signalling

Searching Remote Databases, Please Wait