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Discover how cells reorganize themselves during division
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Discover how cells reorganize themselves during division

A living cell is a bustling metropolis, with countless molecules and proteins flowing through crowded spaces in all directions. Cell division is a big event that completely transforms the landscape. The cell begins to behave like the host of an international competition, reconfiguring entire streets, moving buildings, and rerouting its transportation systems.

For decades, researchers have been captivated by the cell’s ability to organize such a spectacular transformation. At the heart of the process is the microtubule cytoskeleton, a network of fibers that provides structural support and facilitates movement within the cell, ensuring proper chromosome segregation. Errors in cell division can lead to a wide range of diseases and disorders, including cancer or genetic disorders.

Yet despite its crucial importance, the exact mechanisms governing how cells reorganize their interiors during cell division remain a mystery. How does a cell know when and how to reorganize its internal scaffolding? What are the molecular signals that govern these changes? Who are the main players driving all of this?

According to new research, some of the changes come down to a surprisingly simple and elegant system: the flip of a molecular switch. The results are published today in Natural communications by researchers from the Center for Genomic Regulation in Barcelona and the Max Planck Institute for Molecular Physiology in Dortmund.

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

But PRC1 does not act alone. Its activity is tightly controlled to ensure that microtubules assemble at the right time and place. The protein is controlled by a process called phosphorylation, in which enzymes add small chemical tags to specific regions of its surface. These molecular beacons can increase or decrease PRC1 activity.

We found that manipulating the phosphorylation state of PRC1 can induce large-scale transitions between different states of cytoskeletal organization necessary for cell division. Changes only take a few minutes. ยป


Mr Wei Ming Lim, first author of the study and postdoctoral researcher at CRG

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

“We can now create and observe films of a reorganizing cytoskeleton under a microscope, while fast forwarding and rewinding as we wish. This is an important step in the field,” says Professor Thomas Surrey research fellow at ICREA, lead author of the study and researcher at the Genomic Regulation Center of Barcelona.

The new system could eventually shed light on potential therapeutic strategies for conditions in which cell division goes wrong, such as 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, but within them there is a highly organized and very complex system that operates with great precision. With discoveries like these, that complexity begins to reveal itself,” he concludes.

Source:

Journal reference:

Lim, WM, et al. (2024). Regulation of minimal spindle midzone organization by mitotic kinases. Natural communications. doi.org/10.1038/s41467-024-53500-1.

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