Actin turnover protects the cytokinetic contractile ring from structural instability.

Area of Science:

• Cell Biology
• Biophysics

Background:

• Actin turnover is crucial for actomyosin contractile ring function during cell division.
• Cofilin, an actin-binding protein, facilitates actin filament turnover by severing filaments.
• Bridging instabilities, where contractile ring segments detach from the membrane, occur in cofilin mutants, but their cause is unknown.

Purpose of the Study:

• To investigate the role of cofilin in preventing contractile ring instabilities using molecular simulations.
• To elucidate the biophysical mechanisms underlying cofilin's function in maintaining contractile ring integrity.

Main Methods:

• Molecularly explicit simulations of actomyosin contractile rings.
• Analysis of actin filament dynamics, myosin II distribution, and ring tension during simulated constriction.
• Comparison of simulated ring behavior with and without cofilin-mediated actin severing.

Main Results:

• Simulations replicated experimentally observed bridging and reassembly cycles.
• Bridging was associated with segments of low myosin II density.
• Absence of cofilin led to longer actin filaments, increased ring tension (approximately 2-fold), and detachment of actin from myosin II.

Conclusions:

• Cofilin prevents contractile ring bridging by reducing actin filament length and thus ring tension.
• Increased ring tension, caused by the lack of cofilin-mediated severing, drives the detachment of actin from myosin II, leading to bridging.
• Cofilin is critical for maintaining contractile ring structural integrity and preventing cytokinesis failure.