GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment
GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment
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DOI：
10.1093/emboj/20.7.1583
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发表时间：
2001-04-02
期刊：
影响因子：
11.4
通讯作者：
Mayor, S
中科院分区：
文献类型：
--
作者：
Chatterjee, S;Smith, ER;Mayor, S
糖基磷脂酰肌醇（GPI）锚定对于几种蛋白质在其膜运输途径中的功能是重要的。我们之前已经证明，内吞gpi锚定蛋白（GPI-APs）被回收到质膜的速度比其他膜成分慢三倍。最近，我们发现GPI-APs在被递送到一个共同的循环内体室（REC）之前，被递送到缺乏网格蛋白介导途径标记的内吞细胞器。研究表明，gpi - ap回收的限速步骤是它们从REC中缓慢退出；用跨膜蛋白序列替代GPI锚点可消除在该隔室中的保留。使用鞘脂合成抑制剂或在鞘脂合成突变细胞系中消耗内源性鞘脂水平特异性地提高了GPI-APs的内吞再循环率，使其与其他膜成分的再循环率相同。我们之前已经表明，GPI-APs的内吞保留也可以通过胆固醇消耗而减轻。这些发现强烈表明，GPI-APs在REC中的功能保留是通过它们与鞘脂和富含胆固醇的分选平台或“筏”的关联而发生的。
Glycosylphosphatidylinositol (GPI) anchoring is important for the function of several proteins in the context of their membrane trafficking pathways. We have shown previously that endocytosed GPI-anchored proteins (GPI-APs) are recycled to the plasma membrane three times more slowly than other membrane components. Recently, we found that GPI-APs are delivered to endocytic organelles, devoid of markers of the clathrin-mediated pathway, prior to their delivery to a common recycling endosomal compartment (REC). Here we show that the rate-limiting step in the recycling of GPI-APs is their slow exit from the REC; replacement of the GPI anchor with a transmembrane protein sequence abolishes retention in this compartment. Depletion of endogenous sphingolipid levels using sphingolipid synthesis inhibitors or in a sphingolipid-synthesis mutant cell line specifically enhances the rate of endocytic recycling of GPI-APs to that of other membrane components. We have shown previously that endocytic retention of GPI-APs is also relieved by cholesterol depletion. These findings strongly suggest that functional retention of GPI-APs in the REC occurs via their association with sphingolipid and cholesterol-enriched sorting platforms or 'rafts'.