A molecular switch reshapes a dividing cell in minutes

A living cell is a bustling metropolis, with countless molecules and proteins navigating crowded spaces in every direction. Cell division is a grand event which completely transforms the landscape. The cell starts behaving like the host of an international competition, reconfiguring entire streets, relocating buildings and rerouting its transportation systems. 

For decades, researchers have been captivated by the cell's ability to organise such a dramatic transformation. Central to the process is the microtubule cytoskeleton, a network of fibres which provides structural support and facilitates movement within the cell, ensuring that chromosomes are correctly segregated. Errors in cell division can lead to a wide array of diseases and disorders, including cancer or genetic disorders. 

Yet, despite its critical importance, the exact mechanisms governing how cells reorganise their insides during cell division have remained a mystery. How does a cell know when and how to rearrange its internal scaffolding? What are the molecular signals governing these changes? Who are the key players conducting it all? 

According to new research, some of the changes come down to a surprisingly simple and elegant system – the flip of a molecular switch. The findings are published today in Nature Communications by researchers at the Centre for Genomic Regulation in Barcelona and the Max Planck Institute of Molecular Physiology in Dortmund. 

At the heart of the discovery is the protein PRC1. During cell division, PRC1 plays a key role in organising cell division. It crosslinks microtubules, helping to form a structure in the crucial region where microtubules overlap and chromosomes are separated. 

But PRC1 doesn't act alone. Its activity is tightly controlled to ensure that microtubules assemble at the right time and place. The protein is controlled through a process called phosphorylation, where enzymes add small chemical tags to specific regions on its surface. These molecular tags can turn PRC1's activity up or down. 

"We discovered that manipulating the phosphorylation state of PRC1 can induce large-scale transitions between different states of cytoskeleton organization that are needed for cell division. The changes take only a few minutes to complete", explains Dr. Wei Ming Lim, first author of the study and postdoctoral researcher at the CRG. 

The researchers made this discovery by developing a new laboratory system where they can precisely control and even reverse the transitions of the cytoskeletal structures associated with different stages of cell division outside of a living system. The new technology can help the researchers study the fundamental mechanisms governing cell division with greater control and detail than previously possible, and in real time. 

“We can now create and observe movies of a re-organizing cytoskeleton under the microscope, while fast forwarding and rewinding as we please. This is an important milestone in the field,” says ICREA Research Professor Thomas Surrey, senior author of the study and researcher at the Centre for Genomic Regulation in Barcelona. 

The new system can eventually shed light on potential therapeutic strategies for conditions where cell division goes wrong, like cancer. However, for Surrey, the implications of the study are how it inspires a sense of wonder at the sophistication of the natural world. “Cells are incredibly small, yet within them exists a highly organised and very complex system that operates with great precision. With discoveries like these, that complexity is beginning to unravel,” he concludes.