Controlling the location and activation of Rab GTPases

The remarkable degree of specificity with which Rab GTPases recognise distinct subsets of intracellular membranes forms the basis of their ability to act as key cellular regulators, determining the recruitment of downstream effectors to the right membrane at the right time. The molecular mechanisms controlling Rab localisation, however, have proved tricky issues to address. It is becoming increasingly apparent that multiple factors contribute to the specificity of Rab localisation and the close coordination of membrane targeting with Rab activation. With important new insights into the mode of action of the general Rab regulators REP and RabGDI, as well as the demonstration that novel factors such as Yip3/Pra1 act as GDI displacement factors and that signals within Rab proteins contribute to targeting specificity, a better understanding of the concepts governing Rab recruitment and function is now beginning to emerge. The diversity of cellular processes regulated by Rab family members is made possible, not only by the wide range of effectors they recruit, but also by the different mechanisms regulating their own targeting and activation.