Multivalent Rab interactions determine tether-mediated membrane fusion

Autor(en): Luerick, Anna
Gao, Jieqiong
Kuhlee, Anne
Yavavli, Erdal
Langemeyer, Lars
Perz, Angela
Raunser, Stefan
Ungermann, Christian 
Stichwörter: BINDING; Cell Biology; CORVET; ENDOSOME; GTPASE RECOGNITION; HOPS COMPLEX; KINASE; STRUCTURAL BASIS; TRANS-SNARE COMPLEX; VESICLES; YEAST VACUOLE DOCKING
Erscheinungsdatum: 2017
Herausgeber: AMER SOC CELL BIOLOGY
Journal: MOLECULAR BIOLOGY OF THE CELL
Volumen: 28
Ausgabe: 2
Startseite: 322
Seitenende: 332
Zusammenfassung: 
Membrane fusion at endomembranes requires cross-talk between Rab GTPases and tethers to drive SNARE-mediated lipid bilayer mixing. Several tethers have multiple Rab-binding sites with largely untested function. Here we dissected the lysosomal HOPS complex as a tethering complex with just two binding sites for the Rab7-like Ypt7 protein to determine their relevance for fusion. Using tethering and fusion assays combined with HOPS mutants, we show that HOPS-dependent fusion requires both Rab-binding sites, with Vps39 being the stronger Ypt7 interactor than Vps41. The intrinsic amphipathic lipid packaging sensor (ALPS) motif within HOPS Vps41, a target of the vacuolar kinase Yck3, is dispensable for tethering and fusion but can affect tethering if phosphorylated. In combination, our data demonstrate that a multivalent tethering complex uses its two Rab bindings to determine the place of SNARE assembly and thus fusion at endomembranes.
ISSN: 10591524
DOI: 10.1091/mbc.E16-11-0764

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