ArticlePLoS pathogens2019
The mosquito melanization response requires hierarchical activation of non-catalytic clip domain serine protease homologs.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Partial reconstitution of the prophenoloxidase activation system inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Distinct roles of theCurrent research in insect science · 2026Article
- Changes in the Anopheles arabiensis transcriptome and gut microbiota profiles associated with the endosymbiotic Microsporidia MB.BMC genomics · 2025Article
- Dietary L-3,4-dihydroxyphenylalanine (L-DOPA) augments cuticular melanization in Anopheles mosquitos reducing their lifespan and malaria burden.Nature communications · 2025Article
- Fluctuating Warm and Humid Conditions Differentially Impact Immunity and Development in the Malaria Vector Anopheles stephensi.Global change biology · 2025Article
- Morphotype-Specific Antifungal Defense inInsects · 2025Article
- The expanded immunoregulatory protease network in mosquitoes is governed by gene coexpression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Wolbachia elevates host methyltransferase expression and alters the mBMC microbiology · 2025Article
- Advances in the dissection of Anopheles-Plasmodium interactions.PLoS pathogens · 2025Review
- CLIPA protein pairs function as cofactors for prophenoloxidase activation in Anopheles gambiae.Insect biochemistry and molecular biology · 2025Article
- Key gene modules and hub genes associated with pyrethroid and organophosphate resistance in Anopheles mosquitoes: a systems biology approach.BMC genomics · 2024Article
- Late sporogonic stages ofbioRxiv : the preprint server for biology · 2024Article
- Late sporogonic stages ofFrontiers in cellular and infection microbiology · 2024Article
- Serine protease homolog pairs CLIPA4-A6, A4-A7Δ, and A4-A12 act as cofactors for proteolytic activation of prophenoloxidase-2 and -7 in Anopheles gambiae.Insect biochemistry and molecular biology · 2024Article
- Article
- CLIPB4 is a central node in the protease network that regulates humoral immunity in Anopheles gambiae mosquitoes.bioRxiv : the preprint server for biology · 2023Article
- CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes.Journal of innate immunity · 2023Article
- Cleavage activation and functional comparison of Manduca sexta serine protease homologs SPH1a, SPH1b, SPH4, and SPH101 in conjunction with SPH2.Insect biochemistry and molecular biology · 2022Article
- Functional Constraints on Insect Immune System Components Govern Their Evolutionary Trajectories.Molecular biology and evolution · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Serine protease cascades regulate important insect immune responses namely melanization and Toll pathway activation. An important component of these cascades are clip-domain serine protease homologs (cSPHs), which are non-catalytic, but essential for activating the enzyme prophenoloxidase (PPO) in the melanization response during septic infections. The activation of cSPHs requires their proteolytic cleavage, yet factors that control their activation and the complexity of their interactions within these cascades remain unclear. Here, we report the identification of CLIPA28 as a novel immune-related cSPH in the malaria vector Anopheles gambiae. Functional genetic analysis using RNA interference (RNAi) revealed that CLIPA28 is essential for the melanization of Plasmodium berghei parasites in refractory mosquitoes, and for mosquito resistance to fungal infections. We further show, using combined biochemical and genetic approaches, that CLIPA28 is member of a network of at least four cSPHs, whereby members are activated in a hierarchical manner following septic infections. Depletion of the complement-like protein TEP1 abolished the activation of this network after septic infections, whereas, depletion of the serine protease inhibitor 2 (SRPN2) triggered enhanced network activation, even in naïve mosquitoes, culminating in a dramatic reduction in cSPHs hemolymph levels, which paralleled that of PPO. Our data suggest that cSPHs are engaged in complex and multilayered interactions within serine protease cascades that regulate melanization, and identify TEP1 and SRPN2 as two master regulators of the cSPH network.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.