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The ARM repeat domain of hemocyanin interacts with MKK4 to modulate antimicrobial peptides expression
Jude Juventus Aweya1,2, Kaiying Zhuang1,2, Yiqi Liu1,2
1Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou 515063, China.
Abstract:
The mitogen-activated protein kinase (MAPK) intracellular signaling pathway mediates numerous biological processes, including antimicrobial immune response by inducing antimicrobial peptides (AMPs) production. Although MAPK signaling cascade proteins have been identified in penaeid shrimp, their modulation via the MKK4-p38-c-Jun cascade and effect on AMPs production is unknown. Here, we show that hemocyanin (PvHMC), antimicrobial peptides (anti-lipopolysaccharide factor, crustin, and penaeidins), and MKK4-p38-c-Jun cascade proteins are simultaneously induced by pathogens (Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus) in Penaeus vannamei. Intriguingly, knockdown of PvHMC with or without pathogen challenge attenuated the expression of MKK4-p38-c-Jun cascade proteins and their phosphorylation level, which consequently decreased AMPs expression. Further analysis revealed that PvHMC interacts via its armadillo (ARM) repeat domain with PvMKK4 to modulate the p38 MAPK signaling pathway. Thus, the ARM repeat domain enables penaeid shrimp hemocyanin to modulate AMPs expression during antimicrobial response by activating the p38 MAPK signaling pathway.
Insights
Penaeid shrimp hemocyanin modulates antimicrobial peptide production by activating the MKK4-p38-c-Jun signaling pathway. This interaction is crucial for the shrimp
Area of Science:
- Aquatic immunology
- Crustacean molecular biology
- Invertebrate innate immunity
Background:
- Mitogen-activated protein kinase (MAPK) signaling pathways regulate immune responses, including antimicrobial peptide (AMP) production.
- The specific role of the MKK4-p38-c-Jun cascade and hemocyanin in penaeid shrimp immunity remains largely uncharacterized.
Purpose of the Study:
- To investigate the modulation of the MKK4-p38-c-Jun cascade by hemocyanin (PvHMC) in Penaeus vannamei.
- To determine the effect of this interaction on antimicrobial peptide (AMP) production during pathogen challenge.
Main Methods:
- Pathogen challenge experiments with Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus.
- Gene knockdown of Penaeus vannamei hemocyanin (PvHMC) and analysis of MKK4-p38-c-Jun cascade protein expression and phosphorylation.
- Investigation of PvHMC interaction with PvMKK4 using its armadillo (ARM) repeat domain.
Main Results:
- Pathogen challenge simultaneously induced hemocyanin, AMPs, and MKK4-p38-c-Jun cascade proteins in Penaeus vannamei.
- PvHMC knockdown attenuated MKK4-p38-c-Jun cascade activation and consequently decreased AMP expression.
- PvHMC interacts with PvMKK4 via its ARM repeat domain, modulating the p38 MAPK signaling pathway.
Conclusions:
- Penaeid shrimp hemocyanin plays a critical role in innate immunity by modulating the MKK4-p38-c-Jun-mediated p38 MAPK signaling pathway.
- The ARM repeat domain of PvHMC is essential for activating this pathway and enhancing antimicrobial peptide production.
- This study reveals a novel mechanism of immune regulation in penaeid shrimp involving hemocyanin and MAPK signaling.
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