The Journal of cell biology, 2005-07, Vol.170 (1), p.127-139
2005
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- Autor(en) / Beteiligte
- Titel
- Aberrant Lysosomal Carbohydrate Storage Accompanies Endocytic Defects and Neurodegeneration in Drosophila benchwarmer
- Ist Teil von
- The Journal of cell biology, 2005-07, Vol.170 (1), p.127-139
- Ort / Verlag
- United States: Rockefeller University Press
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synoptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synoptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synoptic strength, neuronal viability, and tau neurotoxicity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9525eISSN: 1540-8140DOI: 10.1083/jcb.200412001Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2171373
- Format
- –
- Schlagworte
- Alleles, Animals, Brain research, Carbohydrate Metabolism, Carbohydrates, Carrier Proteins - genetics, Cell Survival - genetics, Cells, Cytoplasmic inclusions, Disease Models, Animal, Drosophila, Drosophila melanogaster - embryology, Drosophila melanogaster - genetics, Drosophila melanogaster - ultrastructure, Drosophila Proteins - genetics, Endocytosis, Endocytosis - genetics, Endosomes - metabolism, Endosomes - pathology, Endosomes - ultrastructure, Female, Genetic mutation, Glycogen Storage Disease - genetics, Glycogen Storage Disease - metabolism, Glycogen Storage Disease - physiopathology, Insects, Larva - growth & development, Larva - metabolism, Larva - ultrastructure, Larvae, Lysosomes - metabolism, Lysosomes - pathology, Lysosomes - ultrastructure, Male, Microscopy, Electron, Transmission, Nerve Degeneration - genetics, Nerve Degeneration - metabolism, Nerve Degeneration - physiopathology, Nervous System Malformations - genetics, Nervous System Malformations - metabolism, Nervous System Malformations - physiopathology, Neuroglia, Neurological disorders, Neuromuscular Junction - metabolism, Neuromuscular Junction - pathology, Neuromuscular Junction - ultrastructure, Neurons, Oogenesis - genetics, Photoreceptors, Protein Transport - genetics, tau Proteins - toxicity, Yolk Sac - metabolism, Yolk Sac - ultrastructure