Please use this identifier to cite or link to this item:
http://hdl.handle.net/20.500.12358/24319
Title | CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells |
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Untitled | |
Abstract |
Juvenile neuronal ceroid lipofuscinosis (JNCL) is a fatal childhood-onset neurodegenerative disorder caused by mutations in ceroid lipofuscinosis neuronal-3 (CLN3), a hydrophobic transmembrane protein of unresolved function. Previous studies indicate blood–brain barrier (BBB) defects in JNCL, and our earlier report showed prominent Cln3 expression in mouse brain endothelium. Here we find that CLN3 is necessary for normal trafficking of the microdomain-associated proteins caveolin-1, syntaxin-6, and multidrug resistance protein 1 (MDR1) in brain endothelial cells. Correspondingly, CLN3-null cells have reduced caveolae, and impaired caveolae- and MDR1-related functions including endocytosis, drug efflux, and cell volume regulation. We also detected an abnormal blood–brain barrier response to osmotic stress in vivo. Evaluation of the plasma membrane with fluorescent sphingolipid probes suggests … |
Type | Journal Article |
Date | 2013 |
Published in | The Journal of Neuroscience |
Series | Volume: 33, Number: 46 |
Publisher | Society for Neuroscience |
Citation | |
Item link | Item Link |
License | ![]() |
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Files in this item | ||
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Farwanah, Hany_12.pdf | 2.113Mb |