Two cells with excessive numbers of centrioles (green) during cell division (DNA shown in cyan, microtubules shown in red). Image credit: Moyer and Holland (CC BY 4.0)
A cell’s DNA is the chemical instruction manual for everything it does. Each cell in our bodies contains over two meters of DNA, which is divided into 46 packages of information called chromosomes. When the body needs to make more cells, for example during growth or repair, existing cells divide in two in order to replicate themselves. This means that they also need to copy all of their DNA and then deliver identical sets of chromosomes to each new cell.
Animal cells use structures called centrioles to help them divide their sets of chromosomes accurately. When cells are about to divide, they make a new set of centrioles by assembling a variety of proteins. This assembly process must be carefully controlled; if too many or too few centrioles are built, cell division errors can occur that lead to the generation of new cells with abnormal numbers of chromosomes.
The enzyme PLK4 helps to assemble centrioles, but its exact role in the construction process has remained largely unknown. For example, how it might modify different components of the centriole, and why this matters, is poorly understood.
By performing cell biological and biochemical experiments using human cells, Moyer and Holland show that PLK4 interacts with a protein called STIL that is found in the central part of the centriole. The modification of STIL at a specific location by PLK4 was needed to link it to another protein in the outer wall of the centriole, and was also necessary for the cells to build new centrioles. Cells in which PLK4 was unable to modify STIL had too few centrioles when they were beginning to divide.
Testing the activity of PLK4 in fruit flies revealed that it plays a similar role as in human cells. This suggests that the modification of STIL by PLK4 is important for normal cell division across different species.
The results presented by Moyer and Holland help us to understand how dividing cells build the complex machinery that enables them to pass on their genetic material accurately. Future work that builds on these findings could provide insight into human diseases, such as brain development disorders and cancer, where centrioles are either defective or present in the wrong number.
