Investigating the effect of microtubule targeting agent Taxol on RhoA signalling

Abstract

The actin cytoskeleton is essential for maintaining cellular shape, intracellular transport, and cell migration, and its dynamic remodelling is tightly regulated by various factors. The crosstalk between the actin cytoskeleton and microtubules is critical for coordinated cell migration, facilitated both by proteins that directly link microtubules to actin networks and by signalling proteins, particularly Rho GTPases. Rho GTPase signalling connects actin and microtubules by influencing the activity of guanine exchange factors and GTPase-activating proteins. GEFH1, a microtubule-associated GEF, becomes activated when released from microtubules during depolymerization, leading to increased RhoA activity. This study explores the effects of the microtubule stabilizer Taxol on RhoA signalling. The results demonstrate that Taxol can displace GEFH1 from microtubules, increase RhoA activation, and enhance downstream effectors, such as actin polymerization and actomyosin contractility. Additionally, this study shows that a microtubule stabilizers without the ability to expand the microtubule lattice does not displace GEFH1 from the microtubule, indicating that Taxol likely displaces GEFH1 through expanding the microtubule lattice. These findings suggest that Taxol's ability to displace GEFH1 from microtubules significantly impacts RhoA signalling, providing new insights into the regulation of cytoskeletal dynamics and the effect of Taxol on these dynamics.