Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling
Open Access
- 23 April 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 453 (7197), 935-939
- https://doi.org/10.1038/nature06901
Abstract
Rapid clearance of apoptotic cells by phagocytosis is essential to prevent inflammation. This paper shows that glial cell phagocytosis in Drosophila requires the interaction of the engulfment receptor Draper with the non-receptor tyrosine kinase Shark through ITAM-like motifs. The Src family kinase Src42a is shown to phosphorylate Draper and thought to promote Shark binding. The cellular machinery promoting phagocytosis of corpses of apoptotic cells is well conserved from worms to mammals. An important component is the Caenorhabditis elegans engulfment receptor CED-1 (ref. 1) and its Drosophila orthologue, Draper2. The CED-1/Draper signalling pathway is also essential for the phagocytosis of other types of ‘modified self’ including necrotic cells3, developmentally pruned axons4,5 and dendrites6, and axons undergoing Wallerian degeneration7. Here we show that Drosophila Shark, a non-receptor tyrosine kinase similar to mammalian Syk and Zap-70, binds Draper through an immunoreceptor tyrosine-based activation motif (ITAM) in the Draper intracellular domain. We show that Shark activity is essential for Draper-mediated signalling events in vivo, including the recruitment of glial membranes to severed axons and the phagocytosis of axonal debris and neuronal cell corpses by glia. We also show that the Src family kinase (SFK) Src42A can markedly increase Draper phosphorylation and is essential for glial phagocytic activity. We propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway. These Draper–Src42A–Shark interactions are strikingly similar to mammalian immunoreceptor–SFK–Syk signalling events in mammalian myeloid and lymphoid cells8,9. Thus, Draper seems to be an ancient immunoreceptor with an extracellular domain tuned to modified self, and an intracellular domain promoting phagocytosis through an ITAM-domain–SFK–Syk-mediated signalling cascade.This publication has 32 references indexed in Scilit:
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