Saposins are proteins (known so far are saposins A, B, C, and D) are small heat-stable molecules that are developed from the precursor protein prosaposin, a 70 kDa glycoprotein. The mature saposins, like prosaposin, activate various lysosomal hydrolases that are invoved in the metabolism of sphingolipids. All 4 saposins are structurally similar, with a central 6-cysteine and a conserved proline formation (Kishimoto Y et al. 1993).
Saposins
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General informationThis section has been translated automatically.
Saposins are generated via their precursor protein prosaposin. The coding gene of the precursor protein prosaposin is located on chromosome 10. Prosaposin is synthesized as a molecule that is posttranslationally shortened and formed into a soluble product by glycolysis.
The proteins saposine-B and C play a particularly important role in the processing of lipid antigens. These proteins are capable of transferring lipids e.g. from a cell membrane to the CD1 complex (Sun Y et al. 2013).
Saposin B molecules aggregate to form soluble saposin-protein-lipid complexes that are able to directly load the CD1 protein, a process that is of central importance in CD1-associated antigen presentation.
Saposin C facilitates CD1-lipid loading in a slightly different way. Saposin C uses a stable membrane-associated topological structure to load CD1-directly with lipid antigens without formation of a soluble saposin-lipid complex.
Thus, saposins use different strategies to load CD1 complexes with lipid antigens. The development of different strategies demonstrates the pathophysiological importance of this antigen processing.
Saposin C deficiency leads to a rare variant of M.Gaucher (E75.2) and is based on a mutation in the prosaposin gene (PSAP). Functionally, this defect leads to an autophagic dysfunction (disturbance of the lysosomes' waste disposal function) and to an accumulation of non-degradable glucocerebrosides.
LiteratureThis section has been translated automatically.
- Kishimoto Y et al (1993) Saposins: structure, function, distribution, and molecular genetics. J Lipid Res 33:1255-1267.
- León L et al (2012) Saposins utilize two strategies for lipid transfer and CD1 antigen presentation. Proc Natl Acad Sci U S A 109:4357-4364.
- Sun Y et al (2013) Tissue-specific effects of saposin A and saposin B on glycosphingolipid degradation in mutant mice. Hum Mol Genet 22:2435-2450.
- Tatti M et al (2013) Cathepsin-mediated regulation of autophagy in saposin C deficiency. Autophagy 9:241-243.