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

Tsai Yi Lu, Jennifer M. MacDonald, Lukas J. Neukomm, Amy E. Sheehan, Rachel Bradshaw, Mary Logan, Marc Freeman

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number14355
JournalNature Communications
Volume8
DOIs
StatePublished - Feb 6 2017

Fingerprint

TNF Receptor-Associated Factor 4
axons
degeneration
Neuroglia
Axons
Drosophila
Phosphotransferases
debris
Debris
activation
Wounds and Injuries
mammals
gene expression
Chemical activation
regulators
clearances
Mammals
src-Family Kinases
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling. / Lu, Tsai Yi; MacDonald, Jennifer M.; Neukomm, Lukas J.; Sheehan, Amy E.; Bradshaw, Rachel; Logan, Mary; Freeman, Marc.

In: Nature Communications, Vol. 8, 14355, 06.02.2017.

Research output: Contribution to journalArticle

Lu, Tsai Yi ; MacDonald, Jennifer M. ; Neukomm, Lukas J. ; Sheehan, Amy E. ; Bradshaw, Rachel ; Logan, Mary ; Freeman, Marc. / Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling. In: Nature Communications. 2017 ; Vol. 8.
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