The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling
Abstract
The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.
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“The possibility that mammalian TLRs recognize non-microbial structures is not unexpected, because the evolutionarily conserved Toll receptor originally identified in Drosophila melanogaster binds to the endogenous ligand Spätzle24.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [24]
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Discrimination of bacterial lipoproteins by Toll-like receptor 6
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Self-citationJPred: a consensus secondary structure prediction server.
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The Toll and Imd pathways are the major regulators of the immune response in Drosophila
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A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway
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“, in addition to its long-known function in embryonic dorso-ventral patternin”
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Self-citationToll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide.
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Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
The host defense of Drosophila melanogaster.
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Self-citationToll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
The immune response of Drosophila
Hoffmann, J. A. (2003) · Nature · doi:10.1038/nature02021 · Cited by 1,553
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Metadata
- Authors
- Weber, A. N. R., Tauszig-Delamasure, S., Hoffmann, J. A., Lelièvre, E., Gascan, H., Ray, K. P., Morse, M. A., Imler, J.-L., & Gay, N. J.
- Affiliations
- University of Cambridge (GB)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Imler, Jean-Luc
- Gay, Nicholas J
- ORCID
- Venue
- Nature Immunology
- Published
- 2003-07-20
- Volume
- 4
- Issue
- 8
- Pages
- 794-800
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2032056947
- Cited by
- 469
- References
- 42
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 17 · 2023: 16 · 2022: 22 · 2021: 29 · 2020: 16 · 2019: 28 · 2018: 18 · 2017: 14 · 2016: 11 · 2015: 18 · 2014: 22 · 2013: 20 · 2012: 17
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- GlaxoSmithKline
- National Institute of Allergy and Infectious Diseases (5P01AI44220-02, P01AI044220)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Spätzle, Toll receptor, Drosophila innate immunity, Toll pathway, cytokine receptor binding, receptor activation, hemolymph injection, Drosophila embryogenesis, innate immune defense
- MeSH terms
- Animals, Drosophila, Protein Binding, Receptors, Cell Surface, Signal Transduction, Protein Structure, Tertiary, Insect Proteins, Drosophila Proteins, Toll-Like Receptors
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