Scientists at IMBA are passionate about discovery and advancing our understanding of biology. They are recognized leaders in their fields, regularly publishing in the top research journals. Contributions from IMBA research groups are of interest to everyone – including scientists, clinicians, and the public. The Research Highlights below summarize some of the most significant discoveries made by IMBA scientists.


21.11.2017

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 mystery. A 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 muscles. However, 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 ingression, actin filaments partially reoriented along the circumference, but they never completely aligned. These 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 network“, says 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", eLife, https://doi.org/10.7554/eLife.30867.001