Fig. 6.

The reconstituted Rab5 regulatory network. The Rab5 activation network of Rab5:GDI, Rabex5:Rabaptin5, and the membrane is intrinsically stochastic and bistable. The switching probability depends on the amount of membrane-bound Rab5:GDP, which in turn is controlled by GDI extraction and the presence of a GDF such as PRA1 that counters the GDI activity. Furthermore, RabGAP-5 can suppress activation by limiting the amount of active Rab5:GTP on the membrane. This effect increases the bistability of the system and can give rise to waves of Rab5 activation on the membrane. The interplay of the network’s components enables the cell to precisely trigger collective Rab activation in space and time.