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Peroxiredoxin 4 Interacts With Domeless and Participates in Antibacterial Immune Response Through the JAK/STAT
Xiao-Qin Ran1, Lin Gao1, Meng Yan1
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.
Abstract:
The JAK/STAT pathway plays an important role in the development and immune responses of animals. In vertebrates, families of cytokines or growth factors act as activators of the JAK/STAT pathway; however, the activators for the JAK/STAT signaling pathway in arthropods are largely unknown. Herein we report a new ligand, peroxiredoxin 4 (Prx4), for the Domeless in the JAK/STAT pathway of shrimp Marsupenaeus japonicus. Prx4 was induced to secrete into the extracellular surroundings upon Vibrio challenge, which then facilitated the anti-Vibrio activity of shrimp by activating the phosphorylation and nuclear translocation of STAT and the expression of STAT-responsive antimicrobial peptides. Blocking the expression of Prx4 in vivo abrogated the activation of the JAK/STAT pathway by Vibrio infection, while injection of Prx4 protein activated the pathway. The interaction between Prx4 and Domeless was proved by immuno-precipitation and protein pull-down assays. Moreover, two cysteine residues in Prx4 that are critical for the interaction and Prx4's anti-Vibrio role were identified, and the binding site in Domeless for Prx4 was proved to be the cytokine-binding homology module fragment. Taken together, our study revealed a new function for Prx4 enzyme and established a new enzyme-type ligand for the activation of the JAK/STAT pathway in an aquatic arthropod.
Insights
Researchers identified peroxiredoxin 4 (Prx4) as a novel enzyme ligand that activates the JAK/STAT pathway in shrimp. This discovery enhances understanding of immune responses in aquatic arthropods against bacterial infections.
Area of Science:
- Immunology
- Molecular Biology
- Crustacean Research
Background:
- The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is crucial for animal development and immunity.
- While cytokine/growth factors activate this pathway in vertebrates, activators in arthropods remain largely unidentified.
Purpose of the Study:
- To identify novel activators of the JAK/STAT pathway in the shrimp *Marsupenaeus japonicus*.
- To elucidate the role of peroxiredoxin 4 (Prx4) in shrimp immunity and JAK/STAT pathway activation.
Main Methods:
- Investigated Prx4 expression and secretion upon *Vibrio* challenge.
- Utilized immunoprecipitation and protein pull-down assays to confirm Prx4-Domeless interaction.
- Performed *in vivo* experiments to block Prx4 expression and assess pathway activation.
Main Results:
- Prx4 is secreted extracellularly upon *Vibrio* infection, activating shrimp anti-Vibrio immunity.
- Prx4 triggers JAK/STAT pathway components (STAT phosphorylation and nuclear translocation) and antimicrobial peptide expression.
- Blocking Prx4 *in vivo* inhibited JAK/STAT activation; Prx4 injection activated the pathway.
Conclusions:
- Peroxiredoxin 4 (Prx4) acts as a novel enzyme-type ligand for the Domeless receptor in the JAK/STAT pathway.
- Identified critical cysteine residues in Prx4 and the binding site on Domeless, revealing mechanisms of interaction.
- Established a new enzyme-ligand interaction for JAK/STAT pathway activation in aquatic arthropods, highlighting Prx4's immune function.
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