Centaurin alpha-1 is a high-affinity PtdIns(3,4,5)P3-binding protein enriched in brain. Sequence analysis indicates centaurin alpha-1 contains two pleckstrin homology domains, ankyrin repeats and an Arf GAP homology domain, placing it in the AZAP family of phosphoinositide-regulated Arf GAPs. Other members of this family are involved in actin cytoskeletal and focal adhesion organization. Recently, it was reported that centaurin alpha-1 expression diminishes cortical actin and decreases Arf6GTP levels consistent with it functioning as an Arf6 GAP in vivo. In the current report, we show that centaurin alpha-1 binds Arfs in vitro and colocalizes with Arf6 and Arf5 in vivo, further supporting an interaction with Arfs. Centaurin alpha-1 expression produces dramatic effects on the actin cytoskeleton, decreasing stress fibers, diminishing cortical actin, and enhancing membrane ruffles and filopodia. Expression of centaurin alpha-1 also enhances cell spreading and disrupts focal adhesion protein localization. The effects of centaurin alpha-1 on stress fibers and cell spreading are reminiscent of those of Arf6GTP. Consistent with this, we show that many of the centaurin alpha-1-induced effects on the actin cytoskeleton and actin-dependent activities do not require GAP activity. Thus, centaurin alpha-1 likely functions via both GAP-dependent and GAP-independent mechanisms to regulate the actin cytoskeleton. Furthermore, we demonstrate that in vitro, centaurin alpha-1 binds F-actin directly, with actin binding activity localized to the PtdIns(3,4,5)P3-binding PH domain. Our data suggest that centaurin alpha-1 may be a component of the neuronal PI 3-kinase cascade that leads to regulation of the neuronal actin cytoskeleton.

中文翻译：

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arf6 GAP甲胎蛋白alpha-1是一种神经元肌动蛋白结合蛋白，它还通过非GAP依赖性活性来调节肌动蛋白的细胞骨架。

Centaurin alpha-1是富含大脑的高亲和力PtdIns（3,4,5）P3结合蛋白。序列分析表明，centaurin alpha-1包含两个pleckstrin同源结构域，锚蛋白重复序列​​和Arf GAP同源结构域，并将其置于磷酸肌醇调节的AZAP家族的Arf GAP中。该家族的其他成员都参与肌动蛋白的细胞骨架和粘着组织。最近，有报道说，人参蛋白α-1表达减少了皮质肌动蛋白并降低了Alf6GTP水平，这与其在体内起着Arf6 GAP的作用相一致。在当前的报告中，我们显示了CENTAURrinα-1在体外与Arfs结合并在体内与Arf6和Arf5共定位，从而进一步支持与Arfs的相互作用。Centaurin alpha-1的表达对肌动蛋白的细胞骨架产生巨大影响，减少了应力纤维，减少了皮质肌动蛋白，并增强膜皱纹和丝状伪足。centaurin alpha-1的表达还增强细胞扩散并破坏粘着斑蛋白的定位。菊粉蛋白α-1对应力纤维和细胞扩散的影响让人联想到Arf6GTP。与此相符，我们表明许多对肌动蛋白细胞骨架和肌动蛋白依赖性活性的百夫灵α-1诱导的作用不需要GAP活性。因此，centaurin alpha-1可能通过GAP依赖性和GAP依赖性机制起作用，以调节肌动蛋白的细胞骨架。此外，我们证明在体外，centaurin alpha-1直接结合F-肌动蛋白，肌动蛋白结合活性位于PtdIns（3,4,5）P3结合PH域。