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Published on: August 22, 2025
Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila
M Lagueux1, E Perrodou, E A Levashina
1Institut de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Propre de Recherche, Strasbourg, France. M.Lagueux@ibmc.u-strasbg.fr
Insights
Drosophila possesses four novel complement-like genes. Their expression increases after immune challenge, suggesting a role in host defense, particularly involving the JAK-STAT and Toll pathways.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- The complement system and alpha(2)-macroglobulin superfamily are crucial in host defense and proteinase regulation.
- Understanding innate immunity in model organisms like Drosophila provides insights into conserved biological mechanisms.
Purpose of the Study:
- To identify and characterize novel genes in Drosophila with similarities to complement C3/alpha(2)-macroglobulin superfamily proteins.
- To investigate the expression patterns and regulation of these genes, particularly in response to immune challenges.
- To explore the involvement of the Janus kinase (JAK) and Toll pathways in the regulation of these complement-like genes.
Main Methods:
- Gene expression analysis in Drosophila during development and after immune challenge.
- Identification of genes encoding proteins homologous to the thiolester-containing protein superfamily.
- Analysis of gene expression in Drosophila mutants for Janus kinase (JAK) hop and Toll pathways.
Main Results:
- Four Drosophila genes encoding proteins similar to complement C3/alpha(2)-macroglobulin superfamily proteins were identified.
- These genes show low-level transcription throughout development, with significant upregulation following immune challenge.
- Constitutive expression of one gene was observed in gain-of-function mutants of JAK hop and Toll, with reduced inducibility in loss-of-function hop mutants.
Conclusions:
- Drosophila expresses novel complement-like proteins potentially involved in host defense.
- The expression of these genes is regulated by immune challenges and influenced by the JAK-STAT and Toll signaling pathways.
- These findings contribute to understanding the innate immune system in Drosophila and the evolution of complement-like proteins.
Abstract:
We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense.
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