The Arf6 GAP centaurin α-1 is a neurolonal actin-binding protein which also functions via GAP-independent activity to regulate te actin cytoskeleton

Academic Article

Abstract

  • Centaurin α-1 is a high-affinity PtdIns(3,4,5)P3-binding protein enriched in brain. Sequence analysis indicates centaurin α-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 α-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 α-1 binds Arfs in vitro and colocalizes with Arf6 and Arf5 in vivo, further supporting an interaction with Arfs. Centaurin α-1 expression produces dramatic effects on the actin cytoskeleton, decreasing stress fibers, diminishing cortical actin, and enhancing membrane ruffles and filopodia. Expression of centaurin α-1 also enhances cell spreading and disrupts focal adhesion protein localization. The effects of centaurin α-1 on stress fibers and cell spreading are reminiscent of those of Arf6GTP. Consistent with this, we show that many of the centaurin α-1-induced effects on the actin cytoskeleton and actin-dependent activities do not require GAP activity. Thus, centaurin α-1 likely functions via both GAP-dependent and GAP-independent mechanisms to regulate the actin cytoskeleton. Furthermore, we demonstrate that in vitro, centaurin α-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 α-1 may be a component of the neuronal PI 3-kinase cascade that leads to regulation of the neuronal actin cytoskeleton.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Thacker E; Kearns B; Chapman C; Hammond J; Howell A; Theibert A
  • Start Page

  • 541
  • End Page

  • 554
  • Volume

  • 83
  • Issue

  • 10