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

Cell. 1997 Sep 19;90(6):1149-59. doi: 10.1016/s0092-8674(00)80380-3.

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, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology
  • Carrier Proteins / genetics
  • Cattle
  • Cloning, Molecular
  • Cytosol / chemistry
  • Cytosol / enzymology
  • Endosomes / chemistry
  • Endosomes / enzymology
  • Fungal Proteins / genetics
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Intracellular Membranes / chemistry
  • Intracellular Membranes / metabolism
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Binding / physiology
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Vesicular Transport Proteins*
  • rab5 GTP-Binding Proteins

Substances

  • Carrier Proteins
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • RABGEF1 protein, human
  • Saccharomyces cerevisiae Proteins
  • VPS9 protein, S cerevisiae
  • Vesicular Transport Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • rab5 GTP-Binding Proteins

Associated data

  • GENBANK/AJ001119
  • GENBANK/U34932