ArticleThe Journal of biological chemistry2010
Molecular mechanism that induces activation of Spätzle, the ligand for the Drosophila Toll receptor.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 87 citations in OpenAlex.
- A possible role of Painless channel in the regulation of immune system activity in Tenebrio molitor L.Scientific reports · 2026Article
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- A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit.eLife · 2024Article
- Cephalic ganglia transcriptomics of the American cockroach Periplaneta americana (Blattodea: Blattidae).Journal of insect science (Online) · 2024Article
- A myeloid differentiation-like protein in partnership with Toll5 from the pest insectProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.PLoS pathogens · 2022Article
- Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.Nature communications · 2022Article
- A Novel Long-Noncoding RNA LncZFAS1 Prevents MPPMolecular neurobiology · 2022Article
- Evolution of Toll, Spatzle and MyD88 in insects: the problem of the Diptera bias.BMC genomics · 2021Article
- Drosophila Hox genes induce melanized pseudo-tumors when misexpressed in hemocytes.Scientific reports · 2021Article
- Article
- A Toll-Spätzle Pathway in the Immune Response ofInsects · 2020Article
- Article
- Airway Mycosis and the Regulation of Type 2 Immunity.Journal of fungi (Basel, Switzerland) · 2020Review
- Article
- Article
- Antimicrobial peptides fromRSC advances · 2019Review
- Selective cleavage of fibrinogen by diverse proteinases initiates innate allergic and antifungal immunity through CD11b.The Journal of biological chemistry · 2019Article
- Spatially Restricted Regulation of Spätzle/Toll Signaling during Cell Competition.Developmental cell · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Drosophila Toll receptor is activated by an endogenous cytokine ligand Spätzle. Active ligand is generated in response to positional cues in embryonic dorso-ventral patterning and microbial pathogens in the insect immune response. Spätzle is secreted as a pro-protein and is processed into an active form by the serine endoproteases Easter and Spätzle-processing enzyme during dorso-ventral patterning and infection, respectively. Here, we provide evidence for the molecular mechanism of this activation process. We show that the Spätzle prodomain masks a predominantly hydrophobic region of Spätzle and that proteolysis causes a conformational change that exposes determinants that are critical for binding to the Toll receptor. We also gather that a conserved sequence motif in the prodomain presents features of an amphipathic helix likely to bind a hydrophobic cleft in Spätzle thereby occluding the putative Toll binding region. This mechanism of activation has a striking similarity to that of coagulogen, a clotting factor of the horseshoe crab, an invertebrate that has changed little in 400 million years. Taken together, our findings demonstrate that an ancient passive defense system has been adapted during evolution and converted for use in a critical pathway of innate immune signaling and embryonic morphogenesis.
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