Title
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A Fat-Facets-Dscam1-JNK pathway enhances axonal growth in development and after injury
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Author
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Abstract
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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. |
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Language
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English
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Source (journal)
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Frontiers in cellular neuroscience
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Publication
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2018
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ISSN
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1662-5102
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DOI
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10.3389/FNCEL.2017.00416
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Volume/pages
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11
(2018)
, 14 p.
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Article Reference
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416
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ISI
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000424485800001
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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