Cytoskeletal disassembly by optogenetic control of RhoA signaling termination

Cellular morphodynamics rely on the adaptive remodeling of the cytoskeleton, which is controlled by a well-coordinated activation and termination of RhoA GTPase signaling. While RhoA activation is extensively studied, the dynamics and molecular mechanisms behind signaling termination are still not well understood. Researchers have developed an optogenetic toolbox on the BcLOV4 platform to control RhoA activation and termination. This system allows for precise regulation of RhoA signaling.

Previous research has attempted to infer the kinetics of GTPase inactivation indirectly, by monitoring the passive recovery from an activated state. However, the direct kinetics of signaling termination has been uncertain. By utilizing the opto-DLC1 component of the toolbox, scientists have discovered that the termination of RhoA signaling is significantly faster than its passive disactivation.

Despite similar signaling amplitudes, opto-DLC1 initiates rapid actin disassembly through the disinhibition of cofilin, while also causing a slower nuclear efflux of YAP compared to opto-GEF11-induced nuclear influx.

These findings introduce a powerful platform technology for controlling protein signaling termination, providing sub-second precision in measuring RhoA activation and termination kinetics. The study reveals a mechanistic asymmetry between signaling activation and termination, which plays a crucial role in maintaining cytoskeletal homeostasis.