Psychosine enhances the shedding of membrane microvesicles: Implications in demyelination in Krabbe's disease

PloS One
Ludovic D'AuriaErnesto R Bongarzone

Abstract

In prior studies, our laboratory showed that psychosine accumulates and disrupts lipid rafts in brain membranes of Krabbe's disease. A model of lipid raft disruption helped explaining psychosine's effects on several signaling pathways important for oligodendrocyte survival and differentiation but provided more limited insight in how this sphingolipid caused demyelination. Here, we have studied how this cationic inverted coned lipid affects the fluidity, stability and structure of myelin and plasma membranes. Using a combination of cutting-edge imaging techniques in non-myelinating (red blood cell), and myelinating (oligodendrocyte) cell models, we show that psychosine is sufficient to disrupt sphingomyelin-enriched domains, increases the rigidity of localized areas in the plasma membrane, and promotes the shedding of membranous microvesicles. The same physicochemical and structural changes were measured in myelin membranes purified from the mutant mouse Twitcher, a model for Krabbe's disease. Areas of higher rigidity were measured in Twitcher myelin and correlated with higher levels of psychosine and of myelin microvesiculation. These results expand our previous analyses and support, for the first time a pathogenic mechanism wh...Continue Reading

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Citations

Jun 2, 2018·Journal of Lipid Research·Claudia VerderioPaola Giussani
Sep 19, 2018·Biomolecules·Hélène PolletDonatienne Tyteca
Nov 30, 2019·Neurochemical Research·Cory R Reiter, Ernesto R Bongarzone
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Jul 25, 2019·Journal of Neuroinflammation·Penelope J HallettOle Isacson
Aug 17, 2019·Traffic·Michel Vidal
Mar 27, 2021·Neuroscience Letters·Allison M BradburyMark S Sands
Mar 23, 2021·Frontiers in Cellular Neuroscience·Rima RebiaiErnesto R Bongarzone
Jun 1, 2021·Journal of Neural Transmission·Daniel Erskine, Johannes Attems

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Methods Mentioned

BETA
flow cytometry
transmission electron microscopy
electron microscopy
confocal microscopy
fluorescence recovery after photobleaching

Software Mentioned

ImageJ
Kaluza

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