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Glycolipid trafficking in Drosophila undergoes pathway switching in response to aberrant cholesterol levels.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2010 Mar 01; Vol. 21 (5), pp. 778-90. Date of Electronic Publication: 2010 Jan 06. - Publication Year :
- 2010
-
Abstract
- In lipid storage diseases, the intracellular trafficking of sphingolipids is altered by conditions of aberrant cholesterol accumulation. Drosophila has been used recently to model lipid storage diseases, but the effects of sterol accumulation on sphingolipid trafficking are not known in the fly, and the trafficking of sphingolipids in general has not been studied in this model organism. Here, we examined the uptake and intracellular distribution of a fluorescent glycolipid analog, BODIPY-lactosyl-ceramide, in Drosophila neurons. The uptake mechanism and intracellular trafficking route of this simple glycolipid are largely conserved. Our principle finding is that cholesterol steers trafficking of the glycolipid between Golgi, lysosome, and recycling compartments. Our analyses support the idea that cholesterol storage in Drosophila triggers a switch in glycolipid trafficking from the biosynthetic to the degradative endolysosomal pathway, whereas cholesterol depletion eliminates recycling of the glycolipid. Unexpectedly, we observe a novel phenomenon we term "hijacking," whereby lactosyl-ceramide diverts the trafficking pathway of an endocytic cargo, dextran, completely away from its lysosomal target. This work establishes that glycolipid trafficking in Drosophila undergoes changes similar to those seen in mammalian cells under conditions of cholesterol storage and therefore validates Drosophila as a suitable model organism in which to study lipid storage diseases.
- Subjects :
- Animals
Antigens, CD chemistry
Boron Compounds chemistry
Endocytosis
Golgi Apparatus metabolism
Green Fluorescent Proteins chemistry
Lactosylceramides chemistry
Lipids chemistry
Lysosomes metabolism
Microscopy, Fluorescence methods
Models, Biological
Models, Chemical
Neurons metabolism
Cholesterol chemistry
Drosophila melanogaster metabolism
Glycolipids chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 21
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 20053687
- Full Text :
- https://doi.org/10.1091/mbc.E09-01-0005