Image showing the DNA (blue) and microtubules (green) of a cell as it undergoes division. The fluorescent molecule (yellow) located at the cell’s centrosomes demonstrates how a new tool known as LoKI is able to direct drugs to specific sites within a cell. Image credit: Paula Bucko (CC BY 4.0)
In order for an animal cell to divide it needs to duplicate its DNA and split this genetic material equally between its daughter cells. This process, also known as mitosis, requires a number of different proteins that work together to coordinate this vital aspect of the cell’s lifecycle. For example, two enzymes known as Polo-like kinase 1 (Plk1) and Aurora A (AurA) accumulate at specialized structures within the cell called centrosomes, where they receive signals from other parts of the cell to promote this process. Plk1 and AurA also operate at other locations in the cell, but it remains unclear whether these proteins have different activities at each individual location.
Current methods for measuring protein activities use drugs or genetic approaches that switch off the target protein’s activities everywhere in the cell. Now, Bucko et al. have developed a new tool named LoKI that is able to direct drugs to specific locations in animal cells to switch off a target protein’s activity only at these sites. The experiments showed that inhibiting the activities of Plk1 and AurA at the centrosomes led to defects that prolonged mitosis.
The new tool developed by Bucko et al. provides a means to more precisely study local events that occur in healthy and diseased cells. This will help us to understand how cancer and other diseases develop and may ultimately lead to new treatments for human patients with these conditions.
