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Molecular & Cellular Biology

Cells divide by contracting a disordered actin filament network

Scientists at IMBA have discovered that the filaments, which generate contractile forces to form a cleavage furrow during cell division, are organized as a randomly oriented network.

During cell division, animal cells assemble and contract an equatorial ring composed of actin and myosin II (actomyosin) – the same proteins required for muscle contraction. The actomyosin ring was discovered over 40 years ago, yet how it contracts has remained a mysteryA classical model proposed that actin and myosin II filaments align along the cell circumference to slide along each other, similar to the well-known mechanism of actomyosin contraction in musclesHowever, the degree of actomyosin network alignment during cytokinesis was unclear, nor was it known whether actin filament alignment was a cause or consequence of contraction.  

To address these longstanding questions, the Gerlich lab at IMBA used an imaging technique that enables to quantify filament orientation – even in dense arrangements when individual filaments cannot be resolved. This showed that the initial contraction of the cell cortex, which leads to the formation of a cleavage furrow, is mediated by a network of randomly oriented actin filaments. Only at later stages of cleavage furrow ingressionactin filaments partially reoriented along the circumference, but they never completely alignedThese findings indicate that disordered actomyosin filament networks generate sufficient mechanical tension for cleavage furrow ingression in dividing cells 

Actin filament alignment at the cell equator might arise from spatially confined polymerization or from motor-driven filament orientation. To distinguish between these possibilities, Gerlich’s group inhibited the motor activity of myosin II and found that it is not required for actin filament accumulation, but is required for filament reorientation within the actomyosin ring. Interestingly, actin filaments remained aligned at the cell equator even after releasing cortical tension by laser microsurgery, revealing a persistent but limited reorganization of the actomyosin networksays Daniel Gerlich, senior researcher at IMBA. Beyond cell division, actomyosin-mediated contractility generates mechanical stress for cellular wound healing, cell migration, and tissue morphogenesis. As a next step it would be exciting to study the relationships between contractile forces and actin network organization in these biological contexts. 

Original Paper
Spira et al., "Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments", eLifehttps://doi.org/10.7554/eLife.30867.001