Flow diagram illustrating the role of ARNO-ARF1 signaling axis in podosome formation. A variety of external factors known to switch cells toward podosome formation activate the ARF GEF, ARNO. ARNO activates ARF1, which in turn induces two major pathways regulating the podosomes. First, ARF1 inhibits Rho, which negatively regulates podosomes via ROCK-dependent formation of myosin-II filaments. Second, ARF1 promotes formation of Arp2/3- and actin-enriched podosome core-like structures associated with matrix degradation sites. The solid arrows represent the direct pathways, and the dashed arrows indicate the existence of unknown intermediate steps in the depicted pathways.