The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7

Curr Biol. 2010 Sep 28;20(18):1654-9. doi: 10.1016/j.cub.2010.08.002.


Rab GTPases coordinate membrane fusion reactions [1]. Rab-GDP requires a guanine nucleotide exchange factor (GEF) for its conversion to the active GTP form. It then binds to effectors such as multimeric tethering complexes and supports fusion [2]. GTPase-activating proteins (GAPs) promote GTP hydrolysis to inactivate the Rab. GEFs are thus critical activators of fusion reactions [3, 4]. The Rab GEF family is diverse, ranging from multimeric complexes [5] to monomeric GEFs [6-9]. At the late endosome, Rab7 activation is critical for endosomal maturation. The yeast Rab7 homolog Ypt7 binds to the homotypic fusion and protein sorting (HOPS) complex [10, 11]. Its subunit Vps39/Vam6 has been proposed as a GEF for Ypt7 [12] and the Rag GTPase Gtr1 [13], but other genetic evidence has implicated the endosomal protein Ccz1 as a GEF for Ypt7 [14]. Ccz1 and its binding partner Mon1 have been linked to endosomal transport and maturation [15-20]. We now provide evidence that the dimeric Mon1-Ccz1 complex is the Rab7/Ypt7 GEF. The Mon1-Ccz1 complex, but neither protein alone, counteracts GAP function in vivo, rescues in vitro fusion of vacuoles carrying Ypt7-GDP, and promotes nucleotide exchange on Ypt7 independently of Vps39/HOPS. Our data indicate that the Mon1-Ccz1 complex triggers endosomal maturation by activating Ypt7 on late endosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endosomes / metabolism*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Multiprotein Complexes / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Vacuoles / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism


  • Ccz1 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • Gyp7 protein, S cerevisiae
  • Mon1 protein, S cerevisiae
  • Multiprotein Complexes
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • ras GTPase-Activating Proteins
  • YPT7 protein, S cerevisiae
  • rab GTP-Binding Proteins