Cited by 469Immune Response and InflammationInvertebrate Immune Response MechanismsNeurobiology and Insect Physiology Research

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Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling

Weber, Alexander N R, Tauszig-Delamasure, Servane, Hoffmann, Jules A, Lelièvre, Eric, Gascan, Hugues, Ray, Keith P, Morse, Mary A, Imler, Jean-Luc, Gay, Nicholas J·2003·Nature Immunology

DOI 10.1038/ni955

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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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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: Weber, Alexander N R
Tauszig-Delamasure, Servane
Hoffmann, Jules A
Lelièvre, Eric
Morse, Mary A
Imler, Jean-Luc
Gay, Nicholas J
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2003-07-20
Volume: 4
Issue: 8
Pages: 794-800
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni955
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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Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling

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