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

Hisanori Horiuchi, Roger Lippé, Heidi M. McBride, Mariantonietta Rubino, Philip Woodman, Harald Stenmark, Vladimir Rybin, Matthias Wilm, Keith Ashman, Matthias Mann, Marino Zerial

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452 Citations (Scopus)

Abstract

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, Rab-aptin-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.

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
JournalCell
Volume90
Issue number6
DOIs
Publication statusPublished - 1997 Sep 19
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Horiuchi, H., Lippé, R., McBride, H. M., Rubino, M., Woodman, P., Stenmark, H., Rybin, V., Wilm, M., Ashman, K., Mann, M., & Zerial, M. (1997). A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell, 90(6), 1149-1159. https://doi.org/10.1016/S0092-8674(00)80380-3