The Mon1-Ccz1 Complex Is the GEF of the Late Endosomal Rab7 Homolog Ypt7

Autor(en): Nordmann, Mirjana
Cabrera, Margarita
Perz, Angela
Broecker, Cornelia
Ostrowicz, Clemens
Engelbrecht-Vandre, Siegfried
Ungermann, Christian 
Stichwörter: ACTIVATION; Biochemistry & Molecular Biology; Biology; Cell Biology; GTPASE; HOMOTYPIC VACUOLE FUSION; Life Sciences & Biomedicine - Other Topics; NUCLEOTIDE EXCHANGE; PROTEIN; REQUIRES; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; TOOTH TYPE 2B; TRANSPORT PATHWAY
Erscheinungsdatum: 2010
Herausgeber: CELL PRESS
Journal: CURRENT BIOLOGY
Volumen: 20
Ausgabe: 18
Startseite: 1654
Seitenende: 1659
Zusammenfassung: 
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.
ISSN: 09609822
DOI: 10.1016/j.cub.2010.08.002

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