ArticleInsect biochemistry and molecular biology2016
CLIPB8 is part of the prophenoloxidase activation system in Anopheles gambiae mosquitoes.
Article in Insect biochemistry and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Partial reconstitution of the prophenoloxidase activation system inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- 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 infection-responsive immune genes suppress Plasmodium falciparum infection in Anopheles stephensi.PLoS pathogens · 2024Article
- An obligate microsporidian parasite modulates defense against opportunistic bacterial infection in the yellow fever mosquitomSphere · 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
- CLIPB4 is a central node in the protease network that regulates humoral immunity in Anopheles gambiae mosquitoes.bioRxiv : the preprint server for biology · 2023Article
- Immune gene expression in the mosquito vector Culex quinquefasciatus during an avian malaria infection.Molecular ecology · 2023Article
- CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes.Journal of innate immunity · 2023Article
- A zone-of-inhibition assay to screen for humoral antimicrobial activity in mosquito hemolymph.Frontiers in cellular and infection microbiology · 2023Article
- Functional Constraints on Insect Immune System Components Govern Their Evolutionary Trajectories.Molecular biology and evolution · 2022Article
- Functional characterization of two clip domain serine proteases in innate immune responses of Aedes aegypti.Parasites & vectors · 2021Article
- Editorial: Unconventional Animal Models in Infectious Disease Research.Frontiers in cellular and infection microbiology · 2021Article
- The CLIP-domain serine protease CLIPC9 regulates melanization downstream of SPCLIP1, CLIPA8, and CLIPA28 in the malaria vector Anopheles gambiae.PLoS pathogens · 2020Article
- Identification of a Conserved Prophenoloxidase Activation Pathway in Cotton BollwormFrontiers in immunology · 2020Article
- CLIPB10 is a Terminal Protease in the Regulatory Network That Controls Melanization in the African Malaria MosquitoFrontiers in cellular and infection microbiology · 2020Article
- The mosquito melanization response requires hierarchical activation of non-catalytic clip domain serine protease homologs.PLoS pathogens · 2019Article
- Mosquito-fungus interactions and antifungal immunity.Insect biochemistry and molecular biology · 2019Review
- Article
- Highly focused transcriptional response of Anopheles coluzzii to O'nyong nyong arbovirus during the primary midgut infection.BMC genomics · 2018Article
- Activation of Aedes aegypti prophenoloxidase-3 and its role in the immune response against entomopathogenic fungi.Insect molecular biology · 2017Article
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4 authors.
Funding
Abstract
In insects and other arthropods the formation of eumelanin (melanization) is a broad spectrum and potent immune response that is used to encapsulate and kill invading pathogens. This immune response is regulated by the activation of prophenoxidase (proPO), which is controlled by proteinase cascades and its serpin inhibitors, together forming the proPO activation system. While the molecular composition of these protease cascades are well understood in insect model systems, major knowledge gaps remain in mosquitoes. Recently, a regulatory unit of melanization in Anopheles gambiae was documented, comprised of the inhibitory serpin-clip-serine proteinase, CLIPB9 and its inhibitor serpin-2 (SRPN2). Partial reversion of SRPN2 phenotypes in melanotic tumor formation and adult survival by SRPN2/CLIPB9 double knockdown suggested other target proteinases of SRPN2 in regulating melanization. Here we report that CLIPB8 supplements the SRPN2/CLIPB9 regulatory unit in controlling melanization in An. gambiae. As with CLIPB9, knockdown of CLIPB8 partially reversed the pleiotropic phenotype induced by SRPN2 silencing with regards to adult survival and melanotic tumor formation. Recombinant SRPN2 protein formed an SDS-stable protein complex with activated recombinant CLIPB8, however did not efficiently inhibit CLIPB8 activity in vitro. CLIPB8 did not directly activate proPO in vitro nor was it able to cleave and activate proCLIPB9. Nevertheless, epistasis analysis using RNAi placed CLIPB8 and CLIPB9 in the same pathway leading to melanization, suggesting that CLIPB8 either acts further upstream of CLIPB9 or is required for activation of a yet to be identified serine proteinase homolog. Taken together, this study identifies CLIPB8 as an additional player in proPO activation cascade and highlights the complexity of the proteinase network that regulates melanization in An. gambiae.
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