A guanine nucleotide exchange factor (GEF) limits Rab GTPase-driven membrane fusion

Autor(en): Langemeyer, Lars
Perz, Angela
Kuemmel, Daniel 
Ungermann, Christian 
Stichwörter: ACTIVATION; Biochemistry & Molecular Biology; COMPLEX; DISPLACEMENT; endosome; GDI; GDP DISSOCIATION INHIBITOR; guanine nucleotide exchange factor (GEF); HOPS; IDENTIFICATION; lysosome; MECHANISM; membrane fusion; Mon1-Ccz1; PRENYLATION; PROTEINS; Rab; Rab7; VACUOLE DOCKING; Ypt7
Erscheinungsdatum: 2018
Herausgeber: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Journal: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 293
Ausgabe: 2
Startseite: 731
Seitenende: 739
Zusammenfassung: 
The identity of organelles in the endomembrane system of any eukaryotic cell critically depends on the correctly localized Rab GTPase, which binds effectors and thus promotes membrane remodeling or fusion. However, it is still unresolved which factors are required and therefore define the localization of the correct fusion machinery. Using SNARE-decorated proteoliposomes that cannot fuse on their own, we now demonstrate that full fusion activity can be achieved by just four soluble factors: a soluble SNARE (Vam7), a guanine nucleotide exchange factor (GEF, Mon1-Ccz1), a Rab-GDP dissociation inhibitor (GDI) complex (prenylated Ypt7-GDI), and a Rab effector complex (HOPS). Our findings reveal that the GEF Mon1-Ccz1 is necessary and sufficient for stabilizing prenylated Ypt7 on membranes. HOPS binding to Ypt7-GTP then drives SNARE-mediated fusion, which is fully GTP-dependent. We conclude that an entire fusion cascade can be controlled by a GEF.
DOI: 10.1074/jbc.M117.812941

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