The arf6 GAP centaurin alpha-1 is a neuronal actin-binding protein which also functions via GAP-independent activity to regulate the actin cytoskeleton

Eur J Cell Biol. 2004 Oct;83(10):541-54. doi: 10.1078/0171-9335-00416.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / metabolism
  • ADP-Ribosylation Factors / physiology*
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Adhesion / physiology
  • Cytoskeleton / metabolism*
  • Focal Adhesions / physiology
  • GTPase-Activating Proteins / metabolism
  • GTPase-Activating Proteins / physiology*
  • Gene Expression
  • HeLa Cells
  • Humans
  • Mice
  • Microfilament Proteins / physiology*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Time Factors


  • ADAP1 protein, human
  • ADP-Ribosylation Factor 6
  • Actins
  • Adap1 protein, rat
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • Arf6 protein, mouse
  • Arf6 protein, rat