AI Article Synopsis
- The Drosophila Toll receptor is activated by the cleaved cytokine Spatzle (Spz), rather than directly responding to microbes like mammalian Toll-like receptors.
- Researchers conducted an in vivo RNAi study to silence 75 Drosophila serine protease genes, searching for those that influence the Toll pathway in response to gram-positive bacteria.
- They identified five new serine proteases that connect recognition proteins to Spz, with four involved in fungal responses and one specifically for gram-positive bacteria, indicating a coordinated signaling pathway.
Article Abstract
Unlike mammalian Toll-like Receptors, the Drosophila Toll receptor does not interact directly with microbial determinants but is rather activated upon binding a cleaved form of the cytokine-like molecule Spatzle (Spz). During the immune response, Spz is thought to be processed by secreted serine proteases (SPs) present in the hemolymph that are activated by the recognition of gram-positive bacteria or fungi . In the present study, we have used an in vivo RNAi strategy to inactivate 75 distinct Drosophila SP genes. We then screened this collection for SPs regulating the activation of the Toll pathway by gram-positive bacteria. Here, we report the identification of five novel SPs that function in an extracellular pathway linking the recognition proteins GNBP1 and PGRP-SA to Spz. Interestingly, four of these genes are also required for Toll activation by fungi, while one is specifically associated with signaling in response to gram-positive bacterial infections. These results demonstrate the existence of a common cascade of SPs upstream of Spz, integrating signals sent by various secreted recognition molecules via more specialized SPs.
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| http://dx.doi.org/10.1016/j.cub.2006.03.020 | DOI Listing |
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