Abstract
Saposin B (Sap B) is a member of a family of four small glycoproteins, Sap A, B, C, and D. Like the other three saposins, Sap B plays a physiological role in the lysosomal degradation of sphingolipids (SLs). Although the interaction of Sap B with SLs has been investigated extensively, that with the main membrane lipid components, namely phospholipids and cholesterol (Chol), is scarcely known. Using large unilamellar vesicles (LUVs) as membrane models, we have now found that Sap B simultaneously extracts from the lipid surface neutral [phosphatidylcholine (PC)] and anionic [phosphatidylinositol (PI)] phospholipids, fewer SLs [ganglioside GM1 (GM1) or cerebroside sulfate (CS)], and no Chol. More PI than SL (GM1 or CS) was solubilized from LUVs containing equal amounts of PI and SLs. An increase in PI level had a poor effect on the Sap B-induced solubilization of GM1 or CS but strongly inhibited that of PC. Sap B was able not only to bind, but also to transfer phospholipids between lipid surfaces. Both the phospholipid binding and transfer activities were optimal at low pH values. These results represent the first biochemical analysis of the Sap B interaction with phospholipids. The capacity of Sap B to bind and transfer phospholipids occurs under conditions mimicking the interior of the late endosomal/lysosomal compartment and thus might have physiological relevance.
Highlights
Saposin B (Sap B) is a member of a family of four small glycoproteins, Sap A, B, C, and D
To better mimic physiological conditions, we examined the interaction of Sap B with SLs inserted into large unilamellar vesicle (LUV) composed of phospholipids and Chol
The formation of complexes between the lipid constituents of LUVs and Sap B was assessed by gel filtration on a Sepharose CL-4B column (Fig. 1)
Summary
Sap B was able to bind, and to transfer phospholipids between lipid surfaces. Saposin B (Sap B) is a member of a family of four small glycoproteins, Sap A, B, C, and D, generated in late endosomes/lysosomes from a single precursor, prosaposin [1, 2] Because of their ability to modulate the lysosomal enzymatic degradation of several sphingolipids (SLs), the saposins play an important role in the pathogenesis of sphingolipidoses, a group of lysosomal storage disorders characterized by SL accumulation [1, 2]. To elucidate in more detail the lipid binding properties of Sap B, we have reexamined its interaction with lipids by inserting SLs into models of biological membranes such as large unilamellar vesicles (LUVs) composed of phospholipids and choles-
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