title: Insulin-like Signaling Promotes Glial Phagocytic Clearance of Degenerating Axons through Regulation of Draper.
abstract: Neuronal injury triggers robust responses from glial cells, including altered gene expression and enhanced phagocytic activity to ensure prompt removal of damaged neurons. The molecular underpinnings of glial responses to trauma remain unclear. Here, we find that the evolutionarily conserved insulin-like signaling (ILS) pathway promotes glial phagocytic clearance of degenerating axons in adult Drosophila. We find that the insulin-like receptor (InR) and downstream effector Akt1 are acutely activated in local ensheathing glia after axotomy and are required for proper clearance of axonal debris. InR/Akt1 activity, it is also essential for injury-induced activation of STAT92E and its transcriptional target draper, which encodes a conserved receptor essential for glial engulfment of degenerating axons. Increasing Draper levels in adult glia partially rescues delayed clearance of severed axons in glial InR-inhibited flies. We propose that ILS functions as a key post-injury communication relay to activate glial responses, including phagocytic activity.
authors: Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
authors: Derek T
authors: DT
authors: Musashe
authors: Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
authors: Maria D
authors: MD
authors: Purice
authors: Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
authors: Sean D
authors: SD
authors: Speese
authors: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 55 North Lake Avenue, Worcester, MA 01605, USA.
authors: Johnna
authors: J
authors: Doherty
authors: Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: loganm@ohsu.edu.
authors: Mary A
authors: MA
authors: Logan
mesh_terms: D000818:Animals; D019771:Axotomy; D002450:Cell Communication; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009832:Olfactory Nerve / Q000601:surgery; D010587:Phagocytosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D008565:Membrane Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; C495322:drpr protein, Drosophila; C094982:InR protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C494917:Akt1 protein, Drosophila; D051057:Proto-Oncogene Proteins c-akt