Phosphatidic acid mediates demyelination in Lpin1 mutant mice
Details
Serval ID
serval:BIB_BA696E2C41F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphatidic acid mediates demyelination in Lpin1 mutant mice
Journal
Genes and Development
ISSN
0890-9369
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
22
Number
12
Pages
1647-1661
Language
english
Abstract
Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent phosphatidate phosphatase (PAP1) enzyme necessary for normal triacylglycerol biosynthesis. The affected animals developed pronounced peripheral neuropathy characterized by myelin degradation, Schwann cell dedifferentiation and proliferation, and a reduction in nerve conduction velocity. The observed demyelination is mediated by endoneurial accumulation of the substrate of the PAP1 enzyme, phosphatidic acid (PA). In addition, we show that PA is a potent activator of the MEK-Erk pathway in Schwann cells, and that this activation is required for PA-induced demyelination. Our results therefore reveal a surprising role for PA in Schwann cell fate determination and provide evidence of a direct link between diseases affecting lipid metabolism and abnormal Schwann cell function
Keywords
Animals , Animals,Newborn , biosynthesis , Cell Differentiation , Cells,Cultured , Demyelinating Diseases , etiology , Gene Expression Regulation , genetics , Lipid Metabolism , metabolism , Mice , Mice,Inbred BALB C , Mice,Knockout , Myelin Sheath , Nuclear Proteins , Organ Specificity , Peripheral Nerves , Phosphatidic Acids , physiology , Protein Isoforms , Proteins , Rats , Rats,Sprague-Dawley , Schwann Cells , Switzerland
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2009 22:13
Last modification date
20/08/2019 15:28