The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function
Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program; Graduate School of Biomedical Sciences, MD/PhD Program
Mitogen-Activated Protein Kinase Kinases; Drosophila Proteins; Neuroglia; Nerve Degeneration
Molecular and Cellular Neuroscience | Neuroscience and Neurobiology
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/Tak1short right arrowMKK4short right arrowdJNKshort right arrowdAP-1 signaling cascade appears to be activation of draper expression after axon injury.Cell Death and Differentiation advance online publication, 26 April 2013; doi:10.1038/cdd.2013.30.
DOI of Published Version
Cell Death Differ. 2013 Sep;20(9):1140-8. doi: 10.1038/cdd.2013.30. Epub 2013 Apr 26. Link to article on publisher's site
Cell death and differentiation
MacDonald, Jennifer M.; Doherty, Johnna E.; Hackett, Rachel; and Freeman, Marc R., "The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function" (2013). University of Massachusetts Medical School Faculty Publications. 70.