Take it and release it: The use of the Rab1 small GTPase at a bacterium's will

Abstract

Successful pathogens are equipped to exploit the signaling pathways of their host cell to establish a niche conducive for their survival and proliferation. One emerging example is the modulation of the small GTPase Rab1 by virulence factors of the intracellular pathogen Legionella pneumophila. Besides proteins that mimic host regulatory factors involved in controlling Rab1 activity, this bacterium temporally locks this small GTPase in its active form by AMPylation. Efficient release of Rab1 from the bacterial phagosome requires deAMPylation prior to being inactivated by the bacterial GAP protein LepB. Whether Rab activity is similarly regulated under native condition is unknown, but it is clear that virulence factors from pathogens can be invaluable tools in dissecting the intricacy of host cellular processes.

Figure 1

A model for the regulation of Rab1 activity by Legionella proteins. (A) SidM associated with the LCV membrane extracts Rab1 from the Rab1-GDI complex and subsequently activates Rab1 by its GEF and AMPylation activity. AMPylated Rab1 becomes inaccessible to GAP proteins such as LepB and TBC1D20, thereby is locked into its active state. (B) The deAMPylase SidD removes the AMP moiety from Rab1, making it accessible to LepB, which stimulates its GTPase activity, leading to the extraction of the inactive Rab1 from the bacterial phagosome by an unknown GDI. The time frame for each event occurring during infection is indicated.