Rab GTPases and membrane identity: Causal or inconsequential?

Rab GTPases are highly conserved components of vesicle trafficking pathways that help to ensure the fusion of a vesicle with a specific target organelle membrane. Specific regulatory pathways promote kinetic proofreading of membrane surfaces by Rab GTPases, and permit accumulation of active Rabs only at the required sites. Emerging evidence indicates that Rab activation and inactivation are under complex feedback control, suggesting that ultrasensitivity and bistability, principles established for other cellular regulatory networks, may also apply to Rab regulation. Such systems can promote the rapid membrane accumulation and removal of Rabs to create time-limited membrane domains with a unique composition, and can explain how Rabs define the identity of vesicle and organelle membranes.