A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function

被引:468
作者
Horiuchi, H
Lippe, R
McBride, HM
Rubino, M
Woodman, P
Stenmark, H
Rybin, V
Wilm, M
Ashman, K
Mann, M
Zerial, M
机构
[1] EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY
[2] UNIV MANCHESTER,SCH BIOL SCI,DIV BIOCHEM,MANCHESTER M13 9PT,LANCS,ENGLAND
[3] NORWEGIAN RADIUM HOSP,DEPT BIOCHEM,N-0310 OSLO,NORWAY
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(00)80380-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The small GTPase Rab5 plays an essential role in endocytic traffic. Rab GDP dissociation inhibitor delivers Rab5 to the membrane, where a nucleotide exchange activity allows recruitment of an effector protein, Rabaptin-5. Here we uncovered a novel 60 kDa Rab5-binding protein, Rabex-5. Rabex-5 forms a tight physical complex with Rabaptin-5, and this complex is essential for endocytic membrane fusion. Sequencing of mammalian Rabex-5 by nanoelectrospray mass spectrometry and cloning revealed striking homology to Vps9p, a yeast protein implicated in endocytic traffic. Rabex-5 displays GDP/GTP exchange activity on Rab5 upon delivery of the GTPase to the membrane. This demonstrates that a soluble exchange factor coupled to a Rab effector translocates from cytosol to the membrane, where the complex stabilizes the GTPase in the active state.
引用
收藏
页码:1149 / 1159
页数:11
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