Multivalent Rab interactions determine tether-mediated membrane fusion.

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.
Mesh Terms:
Binding Sites, Endosomes, Membrane Fusion, Phosphorylation, Protein Binding, Protein Transport, SNARE Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Vacuoles, Vesicular Transport Proteins, rab GTP-Binding Proteins
Mol. Biol. Cell
Date: Jan. 15, 2017
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