Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer

被引:518
作者
Seaman, MNJ
机构
[1] Univ Cambridge, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 2XY, England
[2] Univ Cambridge, Dept Clin Biochem, Cambridge CB2 2XY, England
关键词
retromer; vesicle; retrieval; endosome; Golgi;
D O I
10.1083/jcb.200312034
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Efndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis. Currently, this pathway is poorly understood. Analyses in yeast identified a complex of proteins called "retromer" that is essential for endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p. Retromer comprises five distinct proteins: Vps35p, 29p, 26p, 17p, and 5p, which are conserved in mammals. Here, we show that retromer is required for the efficient retrieval of the cation-independent MPR (CI-MPR). Cells lacking mammalian VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or mislocalization to the plasma membrane. We have localized mVPS26 to multivesicular body endosomes by electron microscopy, and through the use of CD8 reporter protein constructs have examined the effect of loss of mVPS26 upon the trafficking of membrane proteins that cycle between the endosome and the Golgi. The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin.
引用
收藏
页码:111 / 122
页数:12
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