Summary
Previous studies from our laboratory demonstrated that membrane transport along the endocytic pathway is perturbed in a broad collection of sphingolipid storage disease (SLSD) fibroblasts. Namely, we studied a fluorescent analog of lactosylceramide (LacCer), which is endocytosed from the plasma membrane (PM) and subsequently transported to the Golgi complex of normal human skin fibroblasts (HSFs); however, in SLSD cells, transport to the Golgi apparatus is blocked and the lipid accumulates in endosomes. These findings led us to study the endocytic itinerary of LacCer (and other molecules) in normal vs SLSD fibroblasts. In this Chapter we describe the endocytic itinerary of SLs in normal fibroblasts and the perturbation of this lipid trafficking in SLSD fibroblasts. We also summarize our results demonstrating that the observed disruption of membrane trafficking in SLSDs is a consequence of elevated cholesterol which inhibits the function of selected rab proteins. Finally we highlight our attempts to correct the SLSD phenotype by stimulation of membrane traffic in the disease fibroblasts.
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Choudhury, A., Marks, D.L., Pagano, R.E. (2006). Endocytic Trafficking of Glycosphingolipids in Sphingolipidoses. In: Hirabayashi, Y., Igarashi, Y., Merrill, A.H. (eds) Sphingolipid Biology. Springer, Tokyo. https://doi.org/10.1007/4-431-34200-1_23
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DOI: https://doi.org/10.1007/4-431-34200-1_23
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