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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates
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Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles
Suchet Nanda1,2, Abram Calderon1,2, Arya Sachan1
1Fakultät für Chemie und Chemische Biologie, TU Dortmund University, 44227, Dortmund, Germany.
Nature Communications
|December 15, 2023
Summary
Rac activates Rho, coordinating cell protrusions and retractions for migration. This Rac-Rho crosstalk, mediated by Arhgef11/12, guides cell movement and directionality.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Rho GTPases are crucial regulators of cytoskeletal dynamics and cell migration.
- Understanding the crosstalk between Rho GTPases like Rho, Rac, and Cdc42 is essential for deciphering cell motility mechanisms.
Purpose of the Study:
- To directly investigate the spatio-temporal crosstalk between Rho, Rac, and Cdc42 during mammalian cell migration.
- To elucidate the role of Rho-activating GEFs (guanine nucleotide exchange factors) in mediating this crosstalk.
Main Methods:
- Utilized rapid activity perturbation techniques combined with real-time activity measurements in mammalian cells.
- Employed spatio-temporal activity pattern analysis to observe Rho GTPase dynamics.
- Investigated the localization and function of Arhgef11 and Arhgef12 using depletion studies.
Main Results:
- Demonstrated that Rac activity directly stimulates Rho activity.
- Observed precise spatio-temporal coupling: Rac activity at protrusions followed by Rho activation during retraction.
- Identified Arhgef11 and Arhgef12 as key mediators, recruited by active Rac to protrusions/retractions.
- Depletion of Arhgef11/12 impaired crosstalk, altered protrusion-retraction dynamics, reduced migration distance, and increased directionality.
Conclusions:
- Arhgef11 and Arhgef12 coordinate cell protrusion and retraction dynamics by coupling Rac and Rho activity.
- This mechanism facilitates exploratory cell migration and enhances directional movement.
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