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

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

[thumbnail of pubmed-zip/versions/1/package-entries/fncel-11-00416/fncel-11-00416.pdf] Text
pubmed-zip/versions/1/package-entries/fncel-11-00416/fncel-11-00416.pdf - Published Version

Download (3MB)

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
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

Actions (login required)

View Item
View Item