Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Eukaryotic cell motility depends on a dynamic actin cytoskeleton.
• Actin dynamics, including flashes and oscillations, are crucial for cell movement.
• Signaling molecules like Ras and PIP3 interact with actin to form cell protrusions.

Purpose of the Study:

• To investigate how signaling cues regulate actin dynamics for cell polarization and directional movement.
• To understand the role of Gβ protein in controlling actin oscillator coupling.
• To explore the impact of coupling strength on eukaryotic chemotaxis.

Main Methods:

• Utilized an inducible sequestration system to acutely inactivate the Gβ protein subunit.
• Observed F-actin dynamics and cortical oscillations.
• Developed a mathematical model of coupled actin oscillators.

Main Results:

• Acute Gβ inactivation led to persistent, high-amplitude F-actin oscillations.
• Weakly coupled actin oscillators in wild-type cells became strongly synchronized after Gβ inactivation.
• Global coupling impaired sensing of internal and external cues, hindering cell polarization and motility.
• Mathematical modeling indicated that moderate coupling enhances sensitivity to noisy inputs.

Conclusions:

• Gβ protein regulates the coupling strength between actin oscillators, which is essential for cell polarity and directional migration.
• Appropriate coupling strength is critical for efficient chemotaxis.
• Acute loss-of-function approaches are valuable for studying cellular processes masked by genetic compensation.