Differential sorting and fate of endocytosed GPI-anchored proteins
Differential sorting and fate of endocytosed GPI-anchored proteins
复制标题
DOI：
10.1093/emboj/cdf398
复制
发表时间：
2002-08-01
期刊：
影响因子：
11.4
通讯作者：
van der Goot, FG
中科院分区：
文献类型：
--
作者：
Fivaz, M;Vilbois, F;van der Goot, FG
本文以细菌毒素气溶素为探针，研究了内吞糖基磷脂酰肌醇锚定蛋白(GPI-APs)在哺乳动物细胞中的去向。我们利用生化、形态和功能的方法，发现GPI-AP在BHK细胞中沿着内吞途径向下运输，以减少晚期内小体。我们还发现，这种转运与与类筏膜的联系有关，因此脂筏存在于晚期内体中(除了高尔基体和质膜之外)。与之形成鲜明对比的是，内吞的GPI-AP到达CHO细胞中的循环内小体，这种转运与RAFT结合减少相关。然而，当GPI-AP通过将7个或更少的GPI-AP与溶气素突变体聚集在一起而增加它们的RAFT关联性时，GPI-AP被从循环内小体转移到CHO细胞中的晚期内小体。我们得出结论，GPI-AP在不同细胞类型中所遵循的不同内吞途径取决于GPI-AP在脂筏中的停留时间，因此RAFT分配调节了GPI-AP在内吞途径中的分选。
In this paper, we studied the fate of endocytosed glycosylphosphatidyl inositol anchored proteins (GPI-APs) in mammalian cells, using aerolysin, a bacterial toxin that binds to the GPI anchor, as a probe. We find that GPI-APs are transported down the endocytic pathway to reducing late endosomes in BHK cells, using biochemical, morphological and functional approaches. We also find that this transport correlates with the association to raft-like membranes and thus that lipid rafts are present in late endosomes (in addition to the Golgi and the plasma membrane). In marked contrast, endocytosed GPI-APs reach the recycling endosome in CHO cells and this transport correlates with a decreased raft association. GPI-APs are, however, diverted from the recycling endosome and routed to late endosomes in CHO cells, when their raft association is increased by clustering seven or less GPI-APs with an aerolysin mutant. We conclude that the different endocytic routes followed by GPI-APs in different cell types depend on the residence time of GPI-APs in lipid rafts, and hence that raft partitioning regulates GPI-APs sorting in the endocytic pathway.