Cofilin-linked changes in actin filament flexibility promote severing

Area of Science:

• Biophysics
• Molecular and Cell Biology
• Protein-Actin Interactions

Background:

• Cofilin is an actin regulatory protein that enhances actin filament bending and twisting elasticity, leading to filament severing.
• A proposed model suggests that stress accumulation at boundaries between cofilin-decorated (compliant) and bare (stiff) actin filament segments, driven by thermal fluctuations, promotes severing.
• This model predicts a direct correlation between changes in actin filament compliance due to cofilin binding and severing activity.

Purpose of the Study:

• To test the prediction that changes in actin filament compliance caused by cofilin binding influence severing activity.
• To investigate the relationship between the severing activities of cofilactin isoforms and their determined flexural rigidities.

Main Methods:

• Analysis of thermal shape fluctuations to determine the flexural rigidities of actin filaments.
• Evaluation of severing activities of vertebrate and yeast cofilactin.
• Imaging of filament thermal fluctuations to observe severing events and critical angles.

Main Results:

• Yeast actin filaments exhibit greater bending compliance than vertebrate actin filaments.
• Severing activities of cofilactin isoforms correlate with alterations in actin filament flexibility.
• Vertebrate cofilin binds to yeast actin filaments but does not increase their flexibility or cause severing; severing events occur at a critical angle of deformation, which is smaller at boundaries between bare and decorated segments.

Conclusions:

• The study supports a cofilin-severing mechanism where mechanical asymmetry at boundaries between bare and cofilin-decorated actin segments drives stress accumulation and fragmentation.
• This process is analogous to material failure in non-protein materials, highlighting the importance of mechanical properties in protein-mediated filament dynamics.
• Filament flexibility changes, rather than just cofilin binding, are critical determinants of actin filament severing.