Saposin B binds and transfers phospholipids
Saposin B binds and transfers phospholipids
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DOI：
10.1194/jlr.m500547-jlr200
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发表时间：
2006-05-01
影响因子：
6.5
通讯作者：
Vaccaro, Anna Maria
中科院分区：
文献类型：
--
作者：
Ciaffoni, Fiorella;Tatti, Massimo;Vaccaro, Anna Maria
Saposin B（Sap B）是Sap A、B、C和D四种小分子糖蛋白家族的成员。Sap B与其他三种鞘脂激活蛋白一样，在鞘脂的溶酶体降解中发挥生理作用。虽然Sap B与SL的相互作用已被广泛研究，与主要的膜脂质成分，即磷脂和胆固醇（Chol），是很少知道。使用大的单层囊泡（LUV）作为膜模型，我们现在已经发现Sap B同时从脂质表面提取中性[磷脂酰胆碱（PC）]和阴离子[磷脂酰肌醇（PI）]磷脂，更少的SL [神经节苷脂GM 1（GM 1）或腺苷硫酸酯（CS）]，并且没有Chol。从含有等量PI和SL的LUV中溶解的PI多于SL（GM 1或CS）。PI水平的增加对Sap B诱导的GM 1或CS的增溶作用效果不佳，但强烈抑制PC的增溶作用。SAP B不仅能够结合，而且能够在脂质表面之间转移磷脂。磷脂结合和转移活性在低pH值下最佳。这些结果代表了Sap B与磷脂相互作用的第一次生化分析。Sap B结合和转移磷脂的能力发生在模拟晚期内体/溶酶体区室内部的条件下，因此可能具有生理相关性。
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.