ИСТИНА

During cell migration, protrusion of the leading edge is driven by the small GTPase Rac1 and the polymerization of Arp2/3-dependent branched actin networks it triggers. Migration persistence and protrusion lifetime are negatively regulated by the Arp2/3 inhibitory protein Arpin. To understand Arpin regulation, we looked for interacting partners and identified both Tankyrases 1 and 2 using a yeast two hybrid screen and immunoprecipitations using full-length Arpin as a bait. Arpin binds to ankyrin repeats of Tankyrases through a site on its acidic tail, which overlaps with the Arp2/3 binding site. Arpin binding induces a conformational change in full-length Tankyrase 1, as revealed by transmission electron microscopy and negative staining. An Arpin mutation that abolishes binding to Tankyrases impaired membrane translocation of Arpin, its interaction with the Arp2/3 complex and its function in inhibiting migration persistence. Arpin activation thus requires its sequential binding to, first, Tankyrase, and, then, to the Arp2/3 complex.