Reversal of Fortune: Do Rab Gtpases Act on the Target Membrane?

The proper targeting and fusion of transport vesicles with the correct membrane is a critical event in the determination of the identity of different compartments within the cell. Work over the last decade has made tremendous progress toward determining a general mechanism by which this occurs. The cornerstones of such a mechanism will have to include two families of proteins: Rab GTPases and SNARE proteins. SNARE proteins are thought to have a central role in catalyzing the fusion of the vesicle with the target membrane (Weber et al. 1998), while Rab GTPases appear to work upstream of this in mediating the initial docking or tethering of the vesicle to the target membrane (Cao et al. 1998; Waters and Pfeffer 1999). To understand the mechanism by which these two classes of proteins collaborate in this...