2004
DOI: 10.1203/01.pdr.0000136152.54638.95
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A Galactosylceramide Binding Domain Is Involved in Trafficking of CLN3 from Golgi to Rafts via Recycling Endosomes

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Cited by 67 publications
(85 citation statements)
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References 62 publications
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“…Notably, we did not observe a significantly altered sensitivity to cell death of the CbCln3 ⌬ex7/8/⌬ex7/8 cells to low dose thapsigargin treatment compared with wild type cells, perhaps due to the changes we observed in the other intracellular Ca 2ϩ stores, which may serve to protect the cells from Ca 2ϩ -mediated excitotoxicity. Chronic CLN3 loss-of-function has also been reported to alter lipid microdomain architecture, which may influence Ca 2ϩ channel complex formation and activity, and it has been demonstrated that glycolipids, such as the gangliosides, can alter SERCA activity (9,24,44,60,61). Hence, future work delineating the role of CLN3 in regulating lipids may shed further light on the altered Ca 2ϩ handling observed in CLN3-deficient cells.…”
Section: Discussionmentioning
confidence: 99%
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“…Notably, we did not observe a significantly altered sensitivity to cell death of the CbCln3 ⌬ex7/8/⌬ex7/8 cells to low dose thapsigargin treatment compared with wild type cells, perhaps due to the changes we observed in the other intracellular Ca 2ϩ stores, which may serve to protect the cells from Ca 2ϩ -mediated excitotoxicity. Chronic CLN3 loss-of-function has also been reported to alter lipid microdomain architecture, which may influence Ca 2ϩ channel complex formation and activity, and it has been demonstrated that glycolipids, such as the gangliosides, can alter SERCA activity (9,24,44,60,61). Hence, future work delineating the role of CLN3 in regulating lipids may shed further light on the altered Ca 2ϩ handling observed in CLN3-deficient cells.…”
Section: Discussionmentioning
confidence: 99%
“…Although the primary function of CLN3 has not yet been fully uncovered it is proposed to play a role in vesicular trafficking because its deficiency leads to altered dis-tribution of endosomal and lysosomal proteins and phospholipids (7)(8)(9)(10)(11)(12), abnormal morphology of endocytic and lysosomal organelles (7,11), lysosomal pH dyshomeostasis (13)(14)(15), and amino acid transport defects (16). The hallmark JNCL storage material containing subunit c accumulates in both autophagosomes and lysosomes implicating further impact of CLN3 deficiency on the autophagy pathway (17).…”
mentioning
confidence: 99%
“…Golgi fragmentation has been linked to neurodegenerative pathways, and GRASP65 can serve as an indicator of cellular disruption (32,55). GRASP65 was associated with raft fraction 3 and the heavier fractions 4 and 5 at both PND21 and 3 months of age.…”
Section: Discussionmentioning
confidence: 99%
“…Although studying rafts in cell lines allows the investigator to examine the raft contribution from a single cell type, using tissue enables the exami-nation of raft dynamics and proteolipid interaction within the organ system as a whole. The dynamic functions of lipid rafts have been reflected in the recent implication that they may be involved in the pathogenesis of many neurodegenerative conditions (30)(31)(32)(33)(34). These studies, as well as raft interactions for signal transduction, membrane trafficking, and endocytosis, emphasize the value of examining whole tissue in the hope of determining regional brain, genetic, or age-specific effects.…”
mentioning
confidence: 99%
“…They further showed that gp120 and Tat induce sphingomyelinase activity by a mechanism involving induction of oxidative stress by CXCR4 activation. gp120 has a galactosylceramide-binding domain, and other proteins with such a domain regulate membrane trafficking from golgi to lipid rafts, 164 suggesting a potential role for perturbed membrane cycling in HIV-1 dementia pathogenesis. Emerging findings suggest that membrane microdomains called lipid rafts play important roles in the pathogenesis of HIV dementia.…”
Section: Lipid Metabolismmentioning
confidence: 99%