The immunological functions of saposins.

Publisher: Academic Press Country of Publication: United States NLM ID: 0370425 Publication Model: Print Cited Medium: Internet ISSN: 1557-8445 (Electronic) Linking ISSN: 00652776 NLM ISO Abbreviation: Adv Immunol Subsets: MEDLINE

Original Publication: New York, NY : Academic Press

Antigen Presentation*; Glycoproteins/*metabolism ; Lysosomes/*metabolism ; Saposins/*metabolism ; Sphingolipids/*metabolism; Antigens, CD1d/analysis ; Endosomes/chemistry ; Endosomes/metabolism ; Glucosylceramidase/metabolism ; Lipid Metabolism ; Lymphocyte Activation ; Natural Killer T-Cells/immunology

Saposins or sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins that are ubiquitously present in lysosomes. SAPs comprise the five molecules saposins A-D and the GM2 activator protein. Saposins are essential for sphingolipid degradation and membrane digestion. On the one hand, they bind the respective hydrolases required to catabolize sphingolipid molecules; on the other hand, saposins can interact with intralysosomal membrane structures to render lipids accessible to their degrading enzymes. Thus, saposins bridge the physicochemical gap between lipid substrate and hydrophilic hydrolases. Accordingly, defects in saposin function can lead to lysosomal lipid accumulation. In addition to their specific functions in sphingolipid metabolism, saposins have membrane-perturbing properties. At the low pH of lysosomes, saposins get protonated and exhibit a high binding affinity for anionic phospholipids. Based on their universal principle to interact with membrane bilayers, we present the immunological functions of saposins with regard to lipid antigen presentation to CD1-restricted T cells, processing of apoptotic bodies for antigen delivery and cross-priming, as well as their potential antimicrobial impact.
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R01 AI083426 United States AI NIAID NIH HHS

0 (Antigens, CD1d)
0 (Glycoproteins)
0 (Saposins)
0 (Sphingolipids)
EC 3.2.1.45 (Glucosylceramidase)

Date Created: 20100601 Date Completed: 20100827 Latest Revision: 20220227

20250114

PMC4030616

10.1016/S0065-2776(10)05002-9

20510729