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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2013 (arch)     Display Documents



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ID: 688599.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2013 (arch)
A Global In Vivo Drosophila RNAi Screen Identifies a Key Role of Ceramide Phosphoethanolamine for Glial Ensheathment of Axons.
Authors:Ghosh, Aniket; Kling, Tina; Snaidero, Nicolas; Sampaio, Julio; Shevchenko, Andrej; Gras, Heribert; Geurten, Bart; Göpfert, Martin; Schulz, Jörg B; Voigt, Aaron; Simons, Mikael
Date of Publication (YYYY-MM-DD):2013
Title of Journal:PLoS Genetics
Volume:9
Issue / Number:12
Sequence Number of Article:e1003980
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Glia are of vital importance for all complex nervous system. One of the many functions of glia is to insulate and provide trophic and metabolic support to axons. Here, using glial-specific RNAi knockdown in Drosophila, we silenced 6930 conserved genes in adult flies to identify essential genes and pathways. Among our screening hits, metabolic processes were highly represented, and genes involved in carbohydrate and lipid metabolic pathways appeared to be essential in glia. One critical pathway identified was de novo ceramide synthesis. Glial knockdown of lace, a subunit of the serine palmitoyltransferase associated with hereditary sensory and autonomic neuropathies in humans, resulted in ensheathment defects of peripheral nerves in Drosophila. A genetic dissection study combined with shotgun high-resolution mass spectrometry of lipids showed that levels of ceramide phosphoethanolamine are crucial for axonal ensheathment by glia. A detailed morphological and functional analysis demonstrated that the depletion of ceramide phosphoethanolamine resulted in axonal defasciculation, slowed spike propagation, and failure of wrapping glia to enwrap peripheral axons. Supplementing sphingosine into the diet rescued the neuropathy in flies. Thus, our RNAi study in Drosophila identifies a key role of ceramide phosphoethanolamine in wrapping of axons by glia.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Lib
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5601
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