The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton.
Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphatidylinositol 4,5-bisphosphate. In this paper, we show that ASAP1 localizes to focal adhesions and cycles with focal adhesion proteins when cells are stimulated to move. Overexpression of ASAP1 altered the morphology of focal adhesions and blocked both cell spreading and formation of dorsal ruffles induced by platelet-derived growth factor (PDGF). On the other hand, ASAP1, with a mutation that disrupted GTPase-activating protein activity, had a reduced effect on cell spreading and increased the number of cells forming dorsal ruffles in response to PDGF. These data support a role for an Arf GTPase-activating protein, ASAP1, as a regulator of cytoskeletal remodeling and raise the possibility that the Arf pathway is a target for PDGF signaling.
Randazzo
P A
PA
Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. randazzo@helix.nih.gov
Andrade
J
J
Miura
K
K
Brown
M T
MT
Long
Y Q
YQ
Stauffer
S
S
Roller
P
P
Cooper
J A
JA
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010957:Plasmids; D016335:Zinc Fingers
D000199:Actins; D002352:Carrier Proteins; D010750:Phosphoproteins