Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling.
Draper/Ced-1/MEGF-10 is an engulfment receptor that promotes clearance of cellular debris in C. elegans, Drosophila and mammals. Draper signals through an evolutionarily conserved Src family kinase cascade to drive cytoskeletal rearrangements and target engulfment through Rac1. Glia also alter gene expression patterns in response to axonal injury but pathways mediating these responses are poorly defined. We show Draper is cell autonomously required for glial activation of transcriptional reporters after axonal injury. We identify TNF receptor associated factor 4 (TRAF4) as a novel Draper binding partner that is required for reporter activation and phagocytosis of axonal debris. TRAF4 and misshapen (MSN) act downstream of Draper to activate c-Jun N-terminal kinase (JNK) signalling in glia, resulting in changes in transcriptional reporters that are dependent on Drosophila AP-1 (dAP-1) and STAT92E. Our data argue injury signals received by Draper at the membrane are important regulators of downstream transcriptional responses in reactive glia.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Tsai-Yi
TY
Lu
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Jennifer M
JM
MacDonald
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Lukas J
LJ
Neukomm
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Amy E
AE
Sheehan
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Rachel
R
Bradshaw
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Mary A
MA
Logan
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Marc R
MR
Freeman
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D053449:TNF Receptor-Associated Factor 4 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D029721:Drosophila Proteins; D008565:Membrane Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D053449:TNF Receptor-Associated Factor 4; D018808:Transcription Factor AP-1; C495322:drpr protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases