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Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling

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  • Tsai-Yi Lu

    (University of Massachusetts Medical School
    Present address: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe St., WBSB 1001, Baltimore, Maryland 21205, USA)

  • Jennifer M. MacDonald

    (University of Massachusetts Medical School)

  • Lukas J. Neukomm

    (University of Massachusetts Medical School)

  • Amy E. Sheehan

    (University of Massachusetts Medical School)

  • Rachel Bradshaw

    (University of Massachusetts Medical School)

  • Mary A. Logan

    (University of Massachusetts Medical School
    Present address: Junger’s Center for Neurosciences Research, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239, USA)

  • Marc R. Freeman

    (University of Massachusetts Medical School
    Present address: Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97239, USA)

Abstract

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.

Suggested Citation

  • Tsai-Yi Lu & Jennifer M. MacDonald & Lukas J. Neukomm & Amy E. Sheehan & Rachel Bradshaw & Mary A. Logan & Marc R. Freeman, 2017. "Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling," Nature Communications, Nature, vol. 8(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14355
    DOI: 10.1038/ncomms14355
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    Cited by:

    1. Yupu Wang & Ruiling Zhang & Sihao Huang & Parisa Tajalli Tehrani Valverde & Meike Lobb-Rabe & James Ashley & Lalanti Venkatasubramanian & Robert A. Carrillo, 2023. "Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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