Key result
Lack of cofilin severing in fission yeast simulations produced ~2-fold longer actin filaments and ~2-fold higher ring tensions, leading to bridging instabilities during cytokinesis.
Why the study?
The origin of bridging instability in cytokinetic contractile rings observed in fission yeast cofilin mutants was unclear.
Cofilin protects the cytokinetic contractile ring from bridging instability by preventing excessive ring tension.
Cofilin may prevent cytokinetic ring instability; leaves open conservation and relevance in mammalian cells.
In common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which segments of the ring peel away from the plasma membrane, forming straight bridges whose ends remain attached to the membrane. The origin of bridging instability is unclear. Here, we used molecularly explicit simulations of contractile rings to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, and the occurrence of bridging in ring segments with low density of the myosin II protein Myo2. The lack of cofilin severing produced ∼2-fold longer filaments and, consequently, ∼2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2, which was anchoring actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by providing protection from bridging, the principal structural threat to contractile rings.
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McDargh et al. (2022) studied Cytokinesis in fission yeast. Lack of cofilin severing vs. Normal cofilin function was evaluated on Bridging instability and ring tension (~2-fold higher ring tensions). Lack of cofilin severing in fission yeast simulations produced ~2-fold longer actin filaments and ~2-fold higher ring tensions, leading to bridging instabilities during cytokinesis.
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