Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration.

Details

Serval ID
serval:BIB_3D569E691EDA
Type
Article: article from journal or magazin.
Collection
Publications
Title
Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Farley J.E., Burdett T.C., Barria R., Neukomm L.J., Kenna K.P., Landers J.E., Freeman M.R.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
06/02/2018
Peer-reviewed
Oui
Volume
115
Number
6
Pages
1358-1363
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C <sub>2</sub> H <sub>2</sub> zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in axon death. Loss of Peb in Drosophila glutamatergic sensory neurons results in either complete preservation of severed axons, or an axon death phenotype where axons fragment into large, continuous segments, rather than completely disintegrate. Peb is expressed in developing and mature sensory neurons, suggesting it is required to establish or maintain their competence to undergo axon death. peb mutant phenotypes can be rescued by human RREB1, and they exhibit dominant genetic interactions with dsarm mutants, linking peb/RREB1 to the axon death signaling cascade. Surprisingly, Peb is only able to fully block axon death signaling in glutamatergic, but not cholinergic sensory neurons, arguing for genetic diversity in axon death signaling programs in different neuronal subtypes. Our findings identify a transcription factor that regulates axon death signaling, and peb mutant phenotypes of partial fragmentation reveal a genetically accessible step in axon death signaling.
Keywords
Animals, Animals, Genetically Modified, Armadillo Domain Proteins/genetics, Armadillo Domain Proteins/metabolism, Axons/metabolism, Axons/pathology, Cholinergic Neurons/pathology, Cytoskeletal Proteins/genetics, Cytoskeletal Proteins/metabolism, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/genetics, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Wallerian Degeneration/genetics, Wallerian Degeneration/metabolism, Wallerian Degeneration/pathology, Wings, Animal/innervation, Wings, Animal/metabolism, Zinc Fingers/genetics, Wallerian degeneration, axon death, axons
Pubmed
Web of science
Open Access
Yes
Create date
07/02/2019 11:20
Last modification date
20/08/2019 14:33
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