Transient Activations of Rac1 at the Lamellipodium Tip Trigger Membrane Protrusion.

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Cell migration relies on dynamic actin networks in the lamellipodium.
• The WAVE regulatory complex (WRC), a Rac1 effector, is crucial for membrane protrusion.
• Previous studies showed complex Rho GTPase activation patterns during cell protrusion.

Purpose of the Study:

• To investigate the spatiotemporal dynamics of Rac1 activation and its role in lamellipodium protrusion.
• To determine how Rac1 activation is localized and regulated at the leading edge of migrating cells.

Main Methods:

• Single particle tracking (SPT) and super-resolution imaging.
• Utilized Rho GTPase loss- and gain-of-function mutants.
• Employed optogenetic activation of Rac1 and Tiam1.

Main Results:

• Rac1 immobilization at the lamellipodium tip correlates with its activation, unlike RhoA.
• Activated Rac1 immobilization depends on effector binding, including WRC.
• Optogenetic activation confirmed Rac1 needs to be activated near the tip for efficient protrusion.

Conclusions:

• Transient Rac1 activation near the lamellipodium tip is essential for WRC binding and actin-based protrusion.
• This localized, short-lived activation allows precise control over actin dynamics during cell migration.