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 language | English (US) |
|---|---|
| Pages (from-to) | 1140-1148 |
| Number of pages | 9 |
| Journal | Cell Death and Differentiation |
| Volume | 20 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2013 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function
AU - MacDonald, J. M.
AU - Doherty, J.
AU - Hackett, R.
AU - Freeman, Marc
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - dJNK
KW - Engulfment
KW - neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=84882276428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882276428&partnerID=8YFLogxK
U2 - 10.1038/cdd.2013.30
DO - 10.1038/cdd.2013.30
M3 - Article
C2 - 23618811
AN - SCOPUS:84882276428
VL - 20
SP - 1140
EP - 1148
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 9
ER -