Arf GTPase regulation through cascade mechanisms and positive feedback loops

Arf GTPases, together with Rab GTPases, are key regulators of intracellular membrane traffic. Their specific membrane targeting and activation are tightly regulated in time and space by guanine nucleotide exchange factors (GEFs). GEFs are multidomain proteins, which are under tight regulation to ensure fully coordinated and accurate membrane traffic events. Recently, two Arf GEFs, Sec7 and Arno, have been shown to be part of Arf GEF cascades similar to the Rab GEF cascades. Both GEFs are autoinhibited in solution and require an active Arf molecule to be recruited to the membrane and to switch to an open conformation. As such, positive feedback loops, whereby the amount of Arf-GTP on a given organelle increases not linearly with time, can be established.