Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes

被引:149
作者
Luhtala, N [1 ]
Odorizzi, G [1 ]
机构
[1] Univ Colorado, Boulder, CO 80309 USA
关键词
endosomes; protein sorting; ubiquitin thiolesterase;
D O I
10.1083/jcb.200403139
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ubiquitination directs the sorting of cell surface receptors and other integral membrane proteins into the multivesicular body (MVB) pathway. Cargo proteins are subsequently deubiquitinated before their enclosure within MVB vesicles. In Saccharomyces cerevisiae, Bro1 functions at a late step of MVB sorting and is required for cargo protein deubiquitination. We show that the loss of Bro1 function is suppressed by the overexpression of DOA4, which encodes the ubiquitin thiolesterase required for the removal of ubiquitin from MVB cargoes. Overexpression of DOA4 restores cargo protein deubiquitination and sorting via the MVB pathway and reverses the abnormal endosomal morphology typical of bro1 mutant cells, resulting in the restoration of multivesicular endosomes. We further demonstrate that Doa4 interacts with Bro1 on endosomal membranes and that the recruitment of Doa4 to endosomes requires Bro1. Thus, our results point to a key role for Bro1 in coordinating the timing and location of deubiquitination by Doa4 in the MVB pathway.
引用
收藏
页码:717 / 729
页数:13
相关论文
共 40 条
[1]   The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways [J].
Amerik, AY ;
Nowak, J ;
Swaminathan, S ;
Hochstrasser, M .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (10) :3365-3380
[2]   The HECT domain ligase itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system [J].
Angers, A ;
Ramjaun, AR ;
McPherson, PS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (12) :11471-11479
[3]   The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function [J].
Babst, M ;
Wendland, B ;
Estepa, EJ ;
Emr, SD .
EMBO JOURNAL, 1998, 17 (11) :2982-2993
[4]   Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body [J].
Babst, M ;
Katzmann, DJ ;
Snyder, WB ;
Wendland, B ;
Emr, SD .
DEVELOPMENTAL CELL, 2002, 3 (02) :283-289
[5]   ESCRT-III: An endosome-associated heterooligomeric protein complex required for MVB sorting [J].
Babst, M ;
Katzmann, DJ ;
Estepa-Sabal, EJ ;
Meerloo, T ;
Emr, SD .
DEVELOPMENTAL CELL, 2002, 3 (02) :271-282
[6]   Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome [J].
Bilodeau, PS ;
Winistorfer, SC ;
Kearney, WR ;
Robertson, AD ;
Piper, RC .
JOURNAL OF CELL BIOLOGY, 2003, 163 (02) :237-243
[7]   Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase [J].
Burda, P ;
Padilla, SM ;
Sarkar, S ;
Emr, SD .
JOURNAL OF CELL SCIENCE, 2002, 115 (20) :3889-3900
[8]   THE CYTOPLASMIC TAIL DOMAIN OF THE VACUOLAR PROTEIN SORTING RECEPTOR VPS1OP AND A SUBSET OF VPS GENE-PRODUCTS REGULATE RECEPTOR STABILITY, FUNCTION, AND LOCALIZATION [J].
CEREGHINO, JL ;
MARCUSSON, EG ;
EMR, SD .
MOLECULAR BIOLOGY OF THE CELL, 1995, 6 (09) :1089-1102
[9]   Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization [J].
Chatellard-Causse, C ;
Blot, B ;
Cristina, N ;
Torch, S ;
Missotten, M ;
Sadoul, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (32) :29108-29115
[10]   Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases [J].
Cooper, AA ;
Stevens, TH .
JOURNAL OF CELL BIOLOGY, 1996, 133 (03) :529-541