Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling

Jennifer S. Ziegenfuss, Romi Biswas, Michelle A. Avery, Kyoungja Hong, Amy E. Sheehan, Yee Guide Yeung, E. Richard Stanley, Marc Freeman

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)935-939
Number of pages5
JournalNature
Volume453
Issue number7197
DOIs
StatePublished - Jun 12 2008
Externally publishedYes

Fingerprint

Sharks
src-Family Kinases
Phagocytosis
Neuroglia
Immunoreceptor Tyrosine-Based Activation Motif
Axons
Cadaver
Drosophila
Phosphorylation
Wallerian Degeneration
Caenorhabditis elegans
Myeloid Cells
Dendrites
Protein-Tyrosine Kinases
Tyrosine
Mammals
Lymphocytes
Ligands
Membranes
Syk Kinase

ASJC Scopus subject areas

  • General

Cite this

Ziegenfuss, J. S., Biswas, R., Avery, M. A., Hong, K., Sheehan, A. E., Yeung, Y. G., ... Freeman, M. (2008). Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature, 453(7197), 935-939. https://doi.org/10.1038/nature06901

Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. / Ziegenfuss, Jennifer S.; Biswas, Romi; Avery, Michelle A.; Hong, Kyoungja; Sheehan, Amy E.; Yeung, Yee Guide; Stanley, E. Richard; Freeman, Marc.

In: Nature, Vol. 453, No. 7197, 12.06.2008, p. 935-939.

Research output: Contribution to journalArticle

Ziegenfuss, JS, Biswas, R, Avery, MA, Hong, K, Sheehan, AE, Yeung, YG, Stanley, ER & Freeman, M 2008, 'Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling', Nature, vol. 453, no. 7197, pp. 935-939. https://doi.org/10.1038/nature06901
Ziegenfuss JS, Biswas R, Avery MA, Hong K, Sheehan AE, Yeung YG et al. Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature. 2008 Jun 12;453(7197):935-939. https://doi.org/10.1038/nature06901
Ziegenfuss, Jennifer S. ; Biswas, Romi ; Avery, Michelle A. ; Hong, Kyoungja ; Sheehan, Amy E. ; Yeung, Yee Guide ; Stanley, E. Richard ; Freeman, Marc. / Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. In: Nature. 2008 ; Vol. 453, No. 7197. pp. 935-939.
@article{1d4a8963209348a68b32ef62b09e34a1,
title = "Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling",
abstract = "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.",
author = "Ziegenfuss, {Jennifer S.} and Romi Biswas and Avery, {Michelle A.} and Kyoungja Hong and Sheehan, {Amy E.} and Yeung, {Yee Guide} and Stanley, {E. Richard} and Marc Freeman",
year = "2008",
month = "6",
day = "12",
doi = "10.1038/nature06901",
language = "English (US)",
volume = "453",
pages = "935--939",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7197",

}

TY - JOUR

T1 - Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling

AU - Ziegenfuss, Jennifer S.

AU - Biswas, Romi

AU - Avery, Michelle A.

AU - Hong, Kyoungja

AU - Sheehan, Amy E.

AU - Yeung, Yee Guide

AU - Stanley, E. Richard

AU - Freeman, Marc

PY - 2008/6/12

Y1 - 2008/6/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=45149101493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45149101493&partnerID=8YFLogxK

U2 - 10.1038/nature06901

DO - 10.1038/nature06901

M3 - Article

VL - 453

SP - 935

EP - 939

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7197

ER -