The immunological functions of saposins.
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.
Program in Cellular and Molecular Medicine at Children's Hospital, Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA, USA.
Alexandre
A
Darmoise
Patrick
P
Maschmeyer
Florian
F
Winau
D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000032:analysis; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D005962:Glucosylceramidase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D050356:Lipid Metabolism; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000276:immunology; D049231:Saposins / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*
D055610:Antigens, CD1d; D006023:Glycoproteins; D049231:Saposins; D013107:Sphingolipids; D005962:Glucosylceramidase