Koch, Marta and Nicolas, Maya and Zschaetzsch, Marlen and de Geest, Natalie and Claeys, Annelies and Yan, Jiekun and Morgan, Matthew J. and Erfurth, Maria-Luise and Holt, Matthew and Schmucker, Dietmar and Hassan, Bassem A. (2018) A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury. Frontiers in Cellular Neuroscience, 11. ISSN 1662-5102
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Abstract
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.
Item Type: | Article |
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Subjects: | East India library > Medical Science |
Depositing User: | Unnamed user with email support@eastindialibrary.com |
Date Deposited: | 02 Jun 2023 06:55 |
Last Modified: | 12 Sep 2024 04:49 |
URI: | http://info.paperdigitallibrary.com/id/eprint/1262 |