The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function

J. M. MacDonald, J. Doherty, R. Hackett, Marc Freeman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1→MKK4→dJNK→dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

Original languageEnglish (US)
Pages (from-to)1140-1148
Number of pages9
JournalCell Death and Differentiation
Volume20
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

Neuroglia
Phosphotransferases
JNK Mitogen-Activated Protein Kinases
Drosophila
Axons
Wounds and Injuries
MAP Kinase Kinase Kinases
Drosophila Proteins
Axotomy
Mitogen-Activated Protein Kinase Kinases
Transcription Factor AP-1
Phagocytosis
Up-Regulation
Inflammation
Gene Expression

Keywords

  • dJNK
  • Engulfment
  • neurodegeneration

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function. / MacDonald, J. M.; Doherty, J.; Hackett, R.; Freeman, Marc.

In: Cell Death and Differentiation, Vol. 20, No. 9, 09.2013, p. 1140-1148.

Research output: Contribution to journalArticle

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