ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Loss of CLN3 in microglia leads to impaired lipid metabolism and myelin turnover.Communications biology · 2024Article
- Article
- Lysosomal alterations and decreased electrophysiological activity in CLN3 disease patient-derived cortical neurons.Disease models & mechanisms · 2022Article
- Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- Altered protein secretion in Batten disease.Disease models & mechanisms · 2021Review
- CLN3, at the crossroads of endocytic trafficking.Neuroscience letters · 2021Article
- Review
- Review
- Current Insights in Elucidation of Possible Molecular Mechanisms of the Juvenile Form of Batten Disease.International journal of molecular sciences · 2020Review
- An iPSC-Derived Neuron Model of CLN3 Disease Facilitates Small Molecule Phenotypic Screening.ACS pharmacology & translational science · 2020Article
- Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retinal pigment epithelium.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Cellular models of Batten disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice.PloS one · 2020Article
- The CLN3 gene and protein: What we know.Molecular genetics & genomic medicine · 2019Review
- Article
- Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann-Pick diseases.BMC medicine · 2019Article
- Lysosomal proteome analysis reveals that CLN3-defective cells have multiple enzyme deficiencies associated with changes in intracellular trafficking.The Journal of biological chemistry · 2019Article
- Review
- Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery.Biomimetics (Basel, Switzerland) · 2018Review
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.