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Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels

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...

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Autores principales: Hortsch, Ralf, Lee, Esther, Erathodiyil, Nandanan, Hebbar, Sarita, Steinert, Steffen, Lee, Jun Yu, Chua, Doreen See Kin, Kraut, Rachel
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828964/
https://www.ncbi.nlm.nih.gov/pubmed/20053687
http://dx.doi.org/10.1091/mbc.E09-01-0005
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author Hortsch, Ralf
Lee, Esther
Erathodiyil, Nandanan
Hebbar, Sarita
Steinert, Steffen
Lee, Jun Yu
Chua, Doreen See Kin
Kraut, Rachel
author_facet Hortsch, Ralf
Lee, Esther
Erathodiyil, Nandanan
Hebbar, Sarita
Steinert, Steffen
Lee, Jun Yu
Chua, Doreen See Kin
Kraut, Rachel
author_sort Hortsch, Ralf
collection PubMed
description 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.
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spelling pubmed-28289642010-05-16 Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels Hortsch, Ralf Lee, Esther Erathodiyil, Nandanan Hebbar, Sarita Steinert, Steffen Lee, Jun Yu Chua, Doreen See Kin Kraut, Rachel Mol Biol Cell Articles 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. The American Society for Cell Biology 2010-03-01 /pmc/articles/PMC2828964/ /pubmed/20053687 http://dx.doi.org/10.1091/mbc.E09-01-0005 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Hortsch, Ralf
Lee, Esther
Erathodiyil, Nandanan
Hebbar, Sarita
Steinert, Steffen
Lee, Jun Yu
Chua, Doreen See Kin
Kraut, Rachel
Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title_full Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title_fullStr Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title_full_unstemmed Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title_short Glycolipid Trafficking in Drosophila Undergoes Pathway Switching in Response to Aberrant Cholesterol Levels
title_sort glycolipid trafficking in drosophila undergoes pathway switching in response to aberrant cholesterol levels
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828964/
https://www.ncbi.nlm.nih.gov/pubmed/20053687
http://dx.doi.org/10.1091/mbc.E09-01-0005
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