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CdGAP associates with actopaxin to regulate integrin-dependent changes in cell morphology and motility
David P LaLonde1, Markus Grubinger, Nathalie Lamarche-Vane
1Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, 13210, USA.
Current Biology : CB
|July 25, 2006
Summary
The focal adhesion protein CdGAP regulates cell migration by interacting with actopaxin, influencing integrin-induced Rho GTPase signaling and cytoskeletal remodeling. This interaction is crucial for cell spreading and lamellipodia formation during migration.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Integrin signaling mediates cell adhesion and migration by regulating cytoskeletal dynamics.
- Rho GTPases control cytoskeleton remodeling and are modulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).
- The precise regulation of GEFs and GAPs in space and time remains poorly understood.
Purpose of the Study:
- To investigate the role of the Cdc42/Rac GAP CdGAP in cell migration.
- To determine the mechanisms by which CdGAP regulates integrin signaling and cytoskeletal organization.
- To elucidate the interaction between CdGAP and focal adhesion proteins.
Main Methods:
- Overexpression of wild-type and mutant CdGAP.
- RNA interference (RNAi) to reduce CdGAP and actopaxin levels.
- Analysis of cell spreading, lamellipodia formation, and cell migration.
- Co-immunoprecipitation to study protein interactions.
Main Results:
- CdGAP localizes to focal adhesions, potentially via binding to actopaxin.
- CdGAP activity is regulated by cell adhesion.
- CdGAP is essential for normal cell spreading, lamellipodia formation, and migration.
- Actopaxin binding to CdGAP is critical for these cellular processes.
Conclusions:
- CdGAP is a key regulator of integrin-induced Rho GTPase signaling to the cytoskeleton.
- The interaction between CdGAP and actopaxin is critical for the spatial and/or temporal regulation of CdGAP.
- Understanding these signaling events provides insight into cell migration in development and disease, including tumor metastasis.
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