Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome

被引:158
作者
Bilodeau, PS
Winistorfer, SC
Kearney, WR
Robertson, AD
Piper, RC
机构
[1] Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA
[3] Univ Iowa, Coll Med, NMR Facil, Iowa City, IA 52242 USA
关键词
endosome; ubiquitin; multivesicular body; lysosome;
D O I
10.1083/jcb.200305007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ubiquitin (Ub) attachment to cell surface proteins causes their lysosomal degradation by incorporating them into lumenal membranes of multivesicular bodies (MVBs). Two yeast endosomal protein complexes have been proposed as Ub-sorting "receptors," the Vps27-Hse1 complex and the ESCRT-1 complex. We used NMR spectroscopy and mutagenesis studies to map the Ub-binding surface for Vps27 and Vps23. Mutations in Ub that ablate only Vps27 binding or Vps23 binding blocked the ability of Ub to serve as an MVB sorting signal, supporting the idea that both the Vps27-Hse1 and ESCRT-1 complexes interact with ubiquitinated cargo. Vps27 also bound Vps23 directly via two PSDP motifs present within the Vps27 COOH terminus. Loss of Vps27-Vps23 association led to less efficient sorting into the endosomal lumen. However, sorting of vacuolar proteases or the overall biogenesis of the MVB were not grossly affected. In contrast, disrupting interaction between Vps27 and Hse1 caused severe defects in carboxy peptidase Y sorting and MVB formation. These results indicate that both Ub-sorting complexes are coupled for efficient recognition of ubiquitinated cargo.
引用
收藏
页码:237 / 243
页数:7
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