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Multivalent Rab interactions determine tether-mediated membrane fusion.


ABSTRACT: 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.

SUBMITTER: Lurick A 

PROVIDER: S-EPMC5231900 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Multivalent Rab interactions determine tether-mediated membrane fusion.

Lürick Anna A   Gao Jieqiong J   Kuhlee Anne A   Yavavli Erdal E   Langemeyer Lars L   Perz Angela A   Raunser Stefan S   Ungermann Christian C  

Molecular biology of the cell 20161116 2


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-bindin  ...[more]

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