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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geprüft am 15.05.2024