IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway
| Autor: | Dominique Didry, Christophe Le Clainche, Mirko Klingauf, Coumaran Egile, Dominik Schlaepfer, Alexey Veligodskiy, Diep Le, Ruth Kroschewski, Katarina Grohmanova, Marie-France Carlier, Aldo Ferrari |
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| Rok vydání: | 2006 |
| Předmět: |
Protein Denaturation
Arp2/3 complex Wiskott-Aldrich Syndrome Protein Neuronal macromolecular substances Microfilament Biochemistry Models Biological Actin remodeling of neurons IQGAP1 Dogs Animals Humans Immunoprecipitation Actin-binding protein Molecular Biology biology Actin remodeling Cell Biology Actins Cell biology Neoplasm Proteins Protein Structure Tertiary Gene Expression Regulation Neoplastic ras GTPase-Activating Proteins Formins Actin-Related Protein 3 Actin-Related Protein 2 biology.protein MDia1 Microtubule-Associated Proteins Protein Binding |
| Zdroj: | The Journal of biological chemistry. 282(1) |
| ISSN: | 0021-9258 |
| Popis: | IQGAP1 is a conserved modular protein overexpressed in cancer and involved in organizing actin and microtubules in motile processes such as adhesion, migration, and cytokinesis. A variety of proteins have been shown to interact with IQGAP1, including the small G proteins Rac1 and Cdc42, actin, calmodulin, beta-catenin, the microtubule plus end-binding proteins CLIP170 (cytoplasmic linker protein) and adenomatous polyposis coli. However, the molecular mechanism by which IQGAP1 controls actin dynamics in cell motility is not understood. Quantitative co-localization analysis and down-regulation of IQGAP1 revealed that IQGAP1 controls the co-localization of N-WASP with the Arp2/3 complex in lamellipodia. Co-immunoprecipitation supports an in vivo link between IQGAP1 and N-WASP. Pull-down experiments and kinetic assays of branched actin polymerization with N-WASP and Arp2/3 complex demonstrated that the C-terminal half of IQGAP1 activates N-WASP by interacting with its BR-CRIB domain in a Cdc42-like manner, whereas the N-terminal half of IQGAP1 antagonizes this activation by association with a C-terminal region of IQGAP1. We propose that signal-induced relief of the autoinhibited fold of IQGAP1 allows activation of N-WASP to stimulate Arp2/3-dependent actin assembly. |
| Databáze: | OpenAIRE |
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