Insight into the structural hierarchy of the protease cascade that regulates the mosquito melanization response

Serine protease cascades regulate important insect immune responses, including melanization and Toll pathway activation. In the context of melanization, central components of these cascades are clip domain serine proteases (CLIPs) including the catalytic, clip domain serine proteases (cSPs) and thei...

Full description

Saved in:
Bibliographic Details
Published in:Microbes and infection 2024-01, Vol.26 (1-2), p.105245, Article 105245
Main Authors: Saab, Sally A, Zhang, Xiufeng, Zeineddine, Suheir, Morejon, Bianca, Michel, Kristin, Osta, Mike A
Format: Article
Language:English
Subjects:
Animals
Anopheles - genetics
Anopheles - metabolism
Anopheles - microbiology
Bacterial Infections
Insect Proteins - genetics
Insect Proteins - metabolism
Serine Endopeptidases - chemistry
Serine Endopeptidases - genetics
Serine Proteases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Serine protease cascades regulate important insect immune responses, including melanization and Toll pathway activation. In the context of melanization, central components of these cascades are clip domain serine proteases (CLIPs) including the catalytic, clip domain serine proteases (cSPs) and their non-catalytic homologs (cSPHs). Here, we define partially the structural hierarchy of An. gambiae cSPs of the CLIPB family, central players in melanization, and characterize their relative contributions to bacterial melanization and to mosquito susceptibility to bacterial infections. Using in vivo genetic analysis we show that the protease cascade branches downstream of the cSPs CLIPB4 and CLIPB17 into two branches one converging on CLIPB10 and the second on CLIPB8. We also show that the contribution of key cSPHs to melanization in vivo in response to diverse microbial challenges is more significant than any of the individual cSPs, possibly due to partial functional redundancy among the latter. Interestingly, we show that the key cSPH CLIPA8 which is essential for the efficient activation cleavage of CLIPBs in vivo is efficiently cleaved itself by several CLIPBs in vitro, suggesting that cSPs and cSPHs regulate signal amplification and propagation in melanization cascades by providing positive reinforcement upstream and downstream of each other.
ISSN:1286-4579
1769-714X
1769-714X
DOI:10.1016/j.micinf.2023.105245