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PMID: 8917582 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 13280-5

Bosio A, Binczek E, Stoffel W

Abstract

The lipid bilayer of the myelin membrane of the central nervous system (CNS) and the peripheral nervous system (PNS) contains the oligodendrocyte- and Schwann cell-specific glycosphingolipids galactocerebrosides (GalC) and GalC-derived sulfatides (sGalC). We have generated a UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse (cgt-/-) with CNS and PNS myelin completely depleted of GalC and derived sGalC. Oligodendrocytes and Schwann cells are unable to restore the structure and function of these galactosphingolipids to maintain the insulator function of the membrane bilayer. The velocity of nerve conduction of homozygous cgt-/- mice is reduced to that of unmyelinated axons. This indicates a severely altered ion permeability of the lipid bilayer. GalC and sGalC are essential for the unperturbed lipid bilayer of the myelin membrane of CNS and PNS. The severe dysmyelinosis leads to death of the cgt-/- mouse at the end of the myelination period.

MeSH Terms
Animals Brain/physiology Gait Galactosylceramides/biosynthesis Galactosyltransferases/deficiency,genetics Ganglioside Galactosyltransferase Lipid Bilayers/metabolism Membrane Lipids/metabolism Mice Mice, Inbred Strains Mice, Knockout Mice, Neurologic Mutants Motor Activity Myelin Sheath/physiology,ultrastructure Optic Nerve/physiology,ultrastructure Sciatic Nerve/physiology,ultrastructure Spinal Cord/physiology,ultrastructure Transcription, Genetic
Chemicals
Galactosylceramides Lipid Bilayers Membrane Lipids Galactosyltransferases Ganglioside Galactosyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bosio A
Institute of Biochemistry I, Medical Faculty, University of Cologne, Germany.
Binczek E
Stoffel W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.13280
Published
1996-11-12
Pages
13280-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24084
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.23.13280 PMC Full Text View journal details
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