Abstract |
Cyclic GMP-AMP synthase (cGAS), which belongs to the nucleotidyltransferase family, recognizes cytosolic DNA and induces the type I interferon (IFN) pathway through the synthesis of the second messenger cGAMP. In this study, porcine cGAS (p-cGAS) was identified and its tissue distribution, subcellular localization, and functions in innate immunity were characterized. The coding sequence of p-cGAS is 1494 bp long, encodes 497 amino acids, and is most similar (74%) to Bos taurus cGAS. p-cGAS mRNA is abundant in the spleen, duodenum, jejunum, and ileum. The subcellular distribution of p-cGAS is not only in the cytosol, but also on the endoplasmic reticulum (ER) membrane. The overexpression of wild-type p-cGAS in porcine kidney epithelial cells, but not its catalytically inactive mutants, induced IFN-β expression, which was dependent on STING and IRF3. However, the downregulation of p-cGAS by RNA interference markedly reduced IFN-β expression after pseudorabies virus (PRV) infection or poly(dA:dT) transfection. These results demonstrate that p-cGAS is an important DNA sensor, required for IFN-β activation.
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Authors | Jiang Wang, Beibei Chu, Lili Du, Yingqian Han, Xuemei Zhang, Shuangshuang Fan, Yueying Wang, Guoyu Yang |
Journal | Molecular immunology
(Mol Immunol)
Vol. 65
Issue 2
Pg. 436-45
(Jun 2015)
ISSN: 1872-9142 [Electronic] England |
PMID | 25765883
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Poly dA-dT
- Interferon-beta
- Nucleotidyltransferases
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Topics |
- Amino Acid Sequence
- Animals
- Cattle
- Cloning, Molecular
- Endoplasmic Reticulum
(genetics, immunology)
- Gene Expression Regulation
(immunology)
- Interferon-beta
(genetics, immunology)
- Intracellular Membranes
(immunology)
- Molecular Sequence Data
- Mutation
- Nucleotidyltransferases
(genetics, immunology)
- Organ Specificity
(genetics, immunology)
- Poly dA-dT
(pharmacology)
- Sequence Homology, Amino Acid
- Swine
(genetics, immunology)
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