Title | Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Authors | Weber ANR, Tauszig-Delamasure S, Hoffmann JA, Lelièvre E, Gascan H, Ray KP, Morse MA, Imler J-L, Gay NJ |
Journal | Nature immunology |
Volume | 4 |
Issue | 8 |
Pagination | 794-800 |
Date Published | 2003 Aug |
ISSN | 1529-2908 |
Keywords | Animals, Drosophila, Drosophila Proteins, Insect Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Cell Surface, Signal Transduction, Toll-Like Receptors |
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. |
DOI | 10.1038/ni955 |
Alternate Journal | Nat. Immunol. |