title: The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7.
abstract: 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.
authors.affiliation: Department of Biology/Chemistry, University of Osnabrück, Germany.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Nordmann
authors.forename: Margarita
authors.initials: M
authors.lastname: Cabrera
authors.forename: Angela
authors.initials: A
authors.lastname: Perz
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bröcker
authors.forename: Clemens
authors.initials: C
authors.lastname: Ostrowicz
authors.forename: Siegfried
authors.initials: S
authors.lastname: Engelbrecht-Vandré
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
mesh_terms: D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C441960:Ccz1 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; C439608:Gyp7 protein, S cerevisiae; C470635:Mon1 protein, S cerevisiae; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020703:ras GTPase-Activating Proteins; C079005:YPT7 protein, S cerevisiae; D020691:rab GTP-Binding Proteins