The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton
The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton
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DOI：
10.1073/pnas.070552297
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Cooper, JA
中科院分区：
文献类型：
--
作者：
Randazzo, PA;Andrade, J;Cooper, JA
Arf家族GTP结合蛋白最好的特点是作为调节膜交通，但最近的研究表明，在细胞骨架组织的额外作用。Centaurin β家族的Arf GTPases激活蛋白ASAP 1（也称为Centaurin β 4）与Arf和另外两种已知的肌动蛋白细胞骨架调节剂（酪氨酸激酶Src和4，5-二磷酸磷脂酰肌醇）结合。在本文中，我们发现ASAP 1定位于粘着斑，并在细胞受到刺激时与粘着斑蛋白发生周期性变化，ASAP 1的过表达改变了粘着斑的形态，并阻止了血小板衍生生长因子（PDGF）诱导的细胞伸展和背褶的形成。另一方面，ASAP 1突变破坏了GTP酶激活蛋白的活性，这些数据支持了Arf GTP酶激活蛋白ASAP 1作为细胞骨架重塑的调节因子的作用，并提高了Arf途径是PDGF信号传导的靶点的可能性。
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 beta 4), 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.