1. Physiological relevance of sphingolipid activator proteins in cultured human fibroblasts.
- Author
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Sadeghlar F, Remmel N, Breiden B, Klingenstein R, Schwarzmann G, and Sandhoff K
- Subjects
- Base Sequence, Cells, Cultured, Endocytosis, Fibroblasts metabolism, G(M1) Ganglioside metabolism, G(M3) Ganglioside metabolism, Globosides metabolism, Glycoproteins deficiency, Glycosphingolipids chemistry, Humans, Molecular Sequence Data, Saposins, Sphingolipid Activator Proteins, Trihexosylceramides metabolism, Glycoproteins metabolism, Glycosphingolipids metabolism
- Abstract
The physiological degradation of several membrane-bound glycosphingolipids (GSLs) by water-soluble lysosomal exohydrolases requires the assistance of sphingolipid activator proteins (SAPs). Four of these SAPs are synthesized from a single precursor protein (prosaposin). Inherited deficiency of this precursor results in a rare disease in humans with an accumulation of ceramide (Cer) and glycolipids such as glucosylceramide and lactosylceramide (LacCer). In a previous study, we have shown that human SAP-D stimulates the lysosomal degradation of Cer in precursor deficient cells. In order to study the role of SAPs (or saposins) A-D in cellular GSL catabolism, we recently investigated the catabolism of exogenously added [(3)H]labeled ganglioside GM1, Forssman lipid, and endogenously [(14)C]labeled GSLs in SAP-precursor deficient human fibroblasts after the addition of recombinant SAP-A, -B, -C and -D. We found that activator protein deficient cells are still able to slowly degrade gangliosides GM1 and GM3, Forssman lipid and globotriaosylceramide to a significant extent, while LacCer catabolism critically depends on the presence of SAPs. The addition of either of the SAPs, SAP-A, SAP-B or SAP-C, resulted in an efficient hydrolysis of LacCer.
- Published
- 2003
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