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

Details

Serval ID
serval:BIB_520313EA02D7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling.
Journal
Nature communications
Author(s)
Lu T.Y., MacDonald J.M., Neukomm L.J., Sheehan A.E., Bradshaw R., Logan M.A., Freeman M.R.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
06/02/2017
Peer-reviewed
Oui
Volume
8
Pages
14355
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Animals, Animals, Genetically Modified, Axons/metabolism, Axons/pathology, Cell Membrane/metabolism, Cell Membrane/pathology, Drosophila Proteins/metabolism, Drosophila melanogaster/metabolism, Female, JNK Mitogen-Activated Protein Kinases/metabolism, Male, Membrane Proteins/metabolism, Nerve Degeneration/metabolism, Nerve Degeneration/pathology, Neuroglia/cytology, Neuroglia/metabolism, Neuroglia/pathology, Phagocytosis, STAT Transcription Factors/metabolism, Signal Transduction/physiology, TNF Receptor-Associated Factor 4/metabolism, Transcription Factor AP-1/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
08/12/2023 9:45
Last modification date
09/12/2023 7:03
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