Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling
Authors
Ziegenfuss, Jennifer S.Biswas, Romi
Avery, Michelle A.
Hong, Kyoungja
Sheehan, Amy E.
Yeung, Yee-Guide
Stanley, E. Richard
Freeman, Marc R.
Student Authors
Jennifer ZiegenfussMichelle Avery
Academic Program
NeuroscienceUMass Chan Affiliations
Graduate School of Biomedical Sciences, Neuroscience ProgramFreeman Lab
Neurobiology
Document Type
Journal ArticlePublication Date
2008-04-25Keywords
Amino Acid Motifs; Animals; Axons; Cell Line; Cell Membrane; Central Nervous System; Drosophila Proteins; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Neuroglia; *Phagocytosis; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Protein Transport; Protein-Tyrosine Kinases; Proto-Oncogene Proteins pp60(c-src); *Signal Transduction; Two-Hybrid System TechniquesNeuroscience and Neurobiology
Metadata
Show full item recordAbstract
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, Draper. The CED-1/Draper signalling pathway is also essential for the phagocytosis of other types of 'modified self' including necrotic cells, developmentally pruned axons and dendrites, and axons undergoing Wallerian degeneration. 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 cells. 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.Source
Nature. 2008 Jun 12;453(7197):935-9. Epub 2008 Apr 23. Link to article on publisher's siteDOI
10.1038/nature06901Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32835PubMed ID
18432193Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nature06901
Scopus Count
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