The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton

Arf family GTP-binding proteins are best characterized as regulators of mem brane traffic, but recent studies indicate an additional role in cytoskelet al organization. An Arf GTPase-activating protein of the centaurin beta fam ily, ASAP1 (also known as centaurin beta 4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphati dylinositol 4,5-bisphosphate. In this paper, we show that ASAP1 localizes t o focal adhesions and cycles with focal adhesion proteins when cells are st imulated to move, Overexpression of ASAP1 altered the morphology of focal a dhesions and blocked both cell spreading and formation of dorsal ruffles in duced by platelet-derived growth factor (PDGF), On the other hand, ASAP1, w ith a mutation that disrupted GTPase-activating protein activity, had a red uced effect on cell spreading and increased the number of cells forming dor sal ruffles in response to PDGF, These data support a role for an Arf GTPas e-activating protein, ASAP1, as a regulator of cytoskeletal remodeling and raise the possibility that the Arf pathway is a target for PDGF signaling.