Model of ARHGAP17 function in invadopodia. (A) During invadopodia assembly/maturation, ARHGAP17 is present at the invadopodia ring, which helps to restrict Cdc42 activity to the invadopodia core. Cdc42 is activated by a specific GEF at the invadopodia core, most likely FGD1, where it promotes actin nucleation through binding to N-WASP and CIP4 and stimulates degradation through its interaction with IQGAP. ARHGAP17 moves to the invadopodia core by binding to CIP4 where it inactivates Cdc42 to promote invadopodia disassembly. (B) A sequential model of recruitment of the invadopodia proteins analyzed in this study. Cdc42 activity promotes the initiation of invadopodia. Early during assembly, TKS5 and CIP4 are recruited to the invadopodia core while ARHGAP17 localizes to the ring shortly after. Invadopodia mature with increased protein recruitment. The ring-to-core translocation of ARHGA17 initiates invadopodia disassembly by inactivating Cdc42 at the core and promoting the dissolution of the invadopodia.