The arf6 GAP centaurin alpha-1 is a neuronal actin-binding protein which also functions via GAP-independent activity to regulate the actin cytoskeleton.
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.
Mesh Terms:
3T3 Cells, ADP-Ribosylation Factors, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Carrier Proteins, Cell Adhesion, Cytoskeleton, Focal Adhesions, GTPase-Activating Proteins, Gene Expression, HeLa Cells, Humans, Mice, Microfilament Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Protein Binding, Sequence Homology, Amino Acid, Time Factors
3T3 Cells, ADP-Ribosylation Factors, Actins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Carrier Proteins, Cell Adhesion, Cytoskeleton, Focal Adhesions, GTPase-Activating Proteins, Gene Expression, HeLa Cells, Humans, Mice, Microfilament Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Protein Binding, Sequence Homology, Amino Acid, Time Factors
Eur. J. Cell Biol.
Date: Oct. 01, 2004
PubMed ID: 15679100
View in: Pubmed Google Scholar
Download Curated Data For This Publication
198059
Switch View:
- Interactions 5