Figure 3.

Two schematics of increasing complexity describe potential molecular events leading to vacuole fusion. (A) A schematic of the known signalling events leading to vacuole fusion. Circles represent species and their complexes. Squares represent events. Arrows into an event indicate the logical requirements for that event to take place. Arrows originating from an event indicate the event’s consequences. The replacement of an arrowhead by a dot indicates that a species is required for an event to take place, but that species is not consumed when the event happens. Thus, PI3P is required for HOPS to be recruited from the cytosol to the membrane (event 1). HOPS may then leave the membrane (event 2) or participate in chaperoning of free SNARE proteins into a trans-SNARE complex (event 3). Finally, the trans-SNARE complex drives fusion activity (event 4). This linear scheme and its cascading series of logical requirements implies that the removal of PI3P can only prevent fusion. (B) Schematic of increased complexity positing the spontaneous dissociation (and reassociation) of a HOPS:trans-SNARE super-complex. Events 1 and 2 are retained from part A. HOPS chaperoning of free SNARES (event 3) results in a HOPS:trans-SNARE super-complex from which HOPS must be removed—if we assume that the trans-SNARE complex is the competent species driving fusion (event 6). The simplest way we can posit for HOPS to be removed is by spontaneous dissociation (event 4). Species that dissociate spontaneously can likely reassociate (event 5).