Arf6 coordinates actin assembly through the WAVE complex, a mechanism usurped by Salmonella to invade host cells

The small GTPase ADP ribosylation factor (Arf) 6 anchors to the plasma membrane, where it coordinates actin filament polymerization to remodel the membrane-associated cytoskeleton in diverse cell processes, yet how Arf6 directs actin polymerization is unknown. By reconstituting membrane-associated actin assembly, we find that Arf6 assembles actin via the WAVE regulatory complex (WRC). In contrast to other Arf family members, which directly bind and activate WRC, Arf6 signaled to WRC indirectly by recruiting the Arf1 activator ARNO to the membrane. Remarkably, we demonstrate this mechanism is hijacked by the pathogen Salmonella that usurped Arf6 and WRC to invade human host cells and establish intracellular infection. This study describes a mechanism for Arf6-driven actin polymerization.