PUBLICATION
Characterization of cGAS homologs in innate and adaptive mucosal immunities in zebrafish gives evolutionary insights into cGAS-STING pathway
- Authors
- Liu, Z.F., Ji, J.F., Jiang, X.F., Shao, T., Fan, D.D., Jiang, X.H., Lin, A.F., Xiang, L.X., Shao, J.Z.
- ID
- ZDB-PUB-200422-109
- Date
- 2020
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34(6): 7786-7809 (Journal)
- Registered Authors
- Fan, Dongdong, Lin, Aifu, Shao, Jian-zhong, Shao, Tong, Xiang, Lixin
- Keywords
- IFN, IgZ, NF-κB, cGAMP
- MeSH Terms
-
- Adaptive Immunity/immunology*
- Animals
- Cell Line
- HEK293 Cells
- Humans
- Immunity, Innate/immunology*
- Immunity, Mucosal/immunology*
- Membrane Proteins/immunology*
- Nucleotidyltransferases/immunology*
- Signal Transduction/immunology*
- Zebrafish/immunology*
- PubMed
- 32285982 Full text @ FASEB J.
Citation
Liu, Z.F., Ji, J.F., Jiang, X.F., Shao, T., Fan, D.D., Jiang, X.H., Lin, A.F., Xiang, L.X., Shao, J.Z. (2020) Characterization of cGAS homologs in innate and adaptive mucosal immunities in zebrafish gives evolutionary insights into cGAS-STING pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 34(6):7786-7809.
Abstract
Cyclic GMP-AMP synthase (cGAS) is one of the most-characterized cytoplasmic DNA sensors in humans and other mammals. However, knowledge about cGAS homologs in nonmammalian species remains limited. In this study, we report the molecular and functional identification of two cGAS homologs, namely, DrcGASa and DrcGASb, from a zebrafish (Danio rerio) model. DrcGASa and DrcGASb share the same overall conservative structural architectures and functional domains/residues to mammalian cGASs. Both homologs synthesized a 2'3'-cGAMP isomer but not a 3'3'-cGAMP isomer via oligomerization in response to DNA stimulation. Overexpression of DrcGASa/b in HEK293T cells and zebrafish embryos significantly activated NF-κB and IFN-I signaling pathways in a STING-dependent manner. Knockdown of DrcGASa or DrSTING impaired such activations, thereby reducing the host innate immunity against bacterial and viral infections. DrcGASa, but not DrcGASb, was involved in immunoglobulin Z-mediated mucosal immunity in gill-associated lymphoid tissue, suggesting differential functions between the two DrcGASs. This reaction was associated with the DrcGAS-DrSTING-IFNφ1 signaling axis in GALT's γδ T cells. Our findings provide experimental evidence that a modern cGAS-STING pathway that mainly participates in IFN-mediated immunity originated from teleost fish based on the functional constraint of cGAS and STING proteins during vertebrate evolution.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping