The HOPS/class C Vps complex tethers membranes by binding to one Rab GTPase in each apposed membrane

Abstract

The HOPS/class C Vps complex, the effector for the yeast vacuolar Rab GTPase Ypt7p, tethers low-curvature membranes by binding to a Rab GTPase in each apposed membrane. This is the first time that the interactions with distinct membranes that give rise to Rab effector–dependent membrane tethering have been identified.

Multivalent Rab interactions determine tether-mediated membrane fusion

“…Based on the structural arrangement of the subunits, current data agree with a model that HOPS binds the Rab Ypt7 at its opposite ends via the subunits Vps41 and Vps39 to cluster membranes (Hickey and Wickner, 2010; Ho and Stroupe, 2015; Orr et al. , 2015, 2016) and thus promotes fusion by chaperoning SNARE assembly via Vps33 (Baker et al.…”

“…, 2010; Ho and Stroupe, 2015). To distinguish between a role of the ALPS motif in promoting tethering and its regulatory role due to selected phosphorylation, we generated a mutant of HOPS lacking the motif.…”

“…, 2012) and for tethering in vitro (Hickey and Wickner, 2010; Ho and Stroupe, 2015; Orr et al. , 2015).…”

“…HOPS thus does not need this motif for functionality. If present, it can be phosphorylated by Yck3, which lowers tethering efficiency in vitro (Figure 2; Hickey and Wickner, 2010; Ho and Stroupe, 2015; Orr et al. , 2015) but not Ypt7-dependent fusion of vacuoles (Figure 5F).…”

The HOPS/Class C Vps Complex Tethers High‐Curvature Membranes via a Direct Protein–Membrane Interaction

“…However, it remains unclear how the tethering activity of HOPS is related to the many interactions in which HOPS can participate. We recently found that HOPS mediates a tethering reaction by binding to a molecule of Ypt7p in each apposed membrane . Here, we now report an investigation of the contribution of the ALPS motif from the Vps41p HOPS subunit to HOPS‐mediated tethering of highly curved liposomes.…”