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- W2035734706 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 microdomain destabilization and enhanced fluidity in CLN3-null cells. In further work we found that application of the glycosphingolipid lactosylceramide to CLN3-deficient cells rescues protein transport and caveolar endocytosis. Last, we show that CLN3 localizes to the trans-Golgi network (TGN) and partitions with buoyant microdomain fractions. We propose that CLN3 facilitates TGN-to-plasma membrane transport of microdomain-associated proteins. Insult to this pathway may underlie BBB dysfunction and contribute to JNCL pathogenesis." @default.
- W2035734706 created "2016-06-24" @default.
- W2035734706 creator A5007309669 @default.
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- W2035734706 creator A5044981665 @default.
- W2035734706 creator A5048490281 @default.
- W2035734706 creator A5083882530 @default.
- W2035734706 date "2013-11-13" @default.
- W2035734706 modified "2023-10-06" @default.
- W2035734706 title "CLN3 Loss Disturbs Membrane Microdomain Properties and Protein Transport in Brain Endothelial Cells" @default.
- W2035734706 cites W1549194476 @default.
- W2035734706 cites W1550967330 @default.
- W2035734706 cites W1551522379 @default.
- W2035734706 cites W1579469490 @default.
- W2035734706 cites W1961955774 @default.
- W2035734706 cites W1964505583 @default.
- W2035734706 cites W1969025660 @default.
- W2035734706 cites W1969461041 @default.
- W2035734706 cites W1969479040 @default.
- W2035734706 cites W1975545686 @default.
- W2035734706 cites W1977004640 @default.
- W2035734706 cites W1979742208 @default.
- W2035734706 cites W1981916955 @default.
- W2035734706 cites W1987899420 @default.
- W2035734706 cites W1992795339 @default.
- W2035734706 cites W1993068092 @default.
- W2035734706 cites W1994266173 @default.
- W2035734706 cites W1994624166 @default.
- W2035734706 cites W1995411277 @default.
- W2035734706 cites W1997619492 @default.
- W2035734706 cites W1999487245 @default.
- W2035734706 cites W2003522077 @default.
- W2035734706 cites W2004296371 @default.
- W2035734706 cites W2008178647 @default.
- W2035734706 cites W2008518851 @default.
- W2035734706 cites W2011845988 @default.
- W2035734706 cites W2016486782 @default.
- W2035734706 cites W2024005516 @default.
- W2035734706 cites W2030727312 @default.
- W2035734706 cites W2037228773 @default.
- W2035734706 cites W2037273860 @default.
- W2035734706 cites W2044116892 @default.
- W2035734706 cites W2044731711 @default.
- W2035734706 cites W2045454822 @default.
- W2035734706 cites W2045857116 @default.
- W2035734706 cites W2051259730 @default.
- W2035734706 cites W2055735933 @default.
- W2035734706 cites W2060334268 @default.
- W2035734706 cites W2060441085 @default.
- W2035734706 cites W2060587494 @default.
- W2035734706 cites W2062478419 @default.
- W2035734706 cites W2068310937 @default.
- W2035734706 cites W2074342421 @default.
- W2035734706 cites W2074703430 @default.
- W2035734706 cites W2075419129 @default.
- W2035734706 cites W2078157157 @default.
- W2035734706 cites W2078663938 @default.
- W2035734706 cites W2079725368 @default.
- W2035734706 cites W2081481124 @default.
- W2035734706 cites W2082075183 @default.
- W2035734706 cites W2085239147 @default.
- W2035734706 cites W2094210380 @default.
- W2035734706 cites W2095535218 @default.
- W2035734706 cites W2097224680 @default.
- W2035734706 cites W2097786975 @default.
- W2035734706 cites W2104290477 @default.
- W2035734706 cites W2104567497 @default.
- W2035734706 cites W2108598406 @default.
- W2035734706 cites W2110412999 @default.
- W2035734706 cites W2112001901 @default.
- W2035734706 cites W2115679330 @default.
- W2035734706 cites W2118089288 @default.
- W2035734706 cites W2119191811 @default.
- W2035734706 cites W2121936687 @default.
- W2035734706 cites W2133394739 @default.
- W2035734706 cites W2135749649 @default.
- W2035734706 cites W2136558879 @default.
- W2035734706 cites W2139319426 @default.
- W2035734706 cites W2141208045 @default.
- W2035734706 cites W2144648087 @default.
- W2035734706 cites W2150801858 @default.
- W2035734706 cites W2151601814 @default.
- W2035734706 cites W2153767710 @default.
- W2035734706 cites W2158603948 @default.
- W2035734706 cites W2160350590 @default.
- W2035734706 cites W2164260884 @default.
- W2035734706 cites W2164565944 @default.
- W2035734706 cites W2165688465 @default.
- W2035734706 cites W2169875798 @default.
- W2035734706 cites W2174649710 @default.
- W2035734706 cites W2286479189 @default.
- W2035734706 cites W4211044441 @default.
- W2035734706 doi "https://doi.org/10.1523/jneurosci.0498-13.2013" @default.
- W2035734706 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3828460" @default.
- W2035734706 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24227717" @default.
- W2035734706 hasPublicationYear "2013" @default.
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