A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducte...

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Bibliographic Details
Published in:Frontiers in cellular neuroscience 2018-02, Vol.11, p.416-416
Main Authors: Koch, Marta, Nicolas, Maya, Zschaetzsch, Marlen, de Geest, Natalie, Claeys, Annelies, Yan, Jiekun, Morgan, Matthew J, Erfurth, Maria-Luise, Holt, Matthew, Schmucker, Dietmar, Hassan, Bassem A
Format: Article
Language:English
Subjects:
3' Untranslated regions
axonal growth
axonal injury
Axonogenesis
Brain research
Cell adhesion & migration
Cell adhesion molecules
Central nervous system
Down's syndrome
Drosophila melanogaster
DSCAM protein
Genes
Genetic analysis
Genetic screening
Insects
Kinases
Life Sciences
Mammals
Neural cell adhesion molecule
Neurobiology
Neurons and Cognition
Neuroscience
post-transcriptional reguylatiopn
Recovery of function
Signal transduction
Trauma
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Summary:Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3'-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism.
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2017.00416