The mystery of the formation of centrioles
Centrioles with “cartwheel” (in colour) in front of an image taken by an electron microscope
Centrioles enable human cells to “perceive” their environment, to communicate with each other, and to move around. But how are they formed? Scientists from EPFL and the Paul Scherrer Institute answer this 50-year-old question on cellular biology.
Centrioles appeared very early in the process of evolution. They are present in eukaryotes, which encompass single-cell organisms, as well as in all animals, including humans. They perform basic functions, in particular in cell division, and are also involved in the formation of cilia and flagella. The cilia perform – among other functions – a cleaning role in the airways, while the flagella are responsible for the mobility of spermatozoa.
A cartwheel with nine spokes
Centrioles were discovered about 50 years ago, and their structure is now well understood. On images from an electron microscope, we can see that the centrioles are organized around a structure having the shape of a cartwheel, hence the name. Nine triplets of microtubules are organized in a ring, and form a cylinder. This is why biologists speak about a “nine fold symmetry”. The “cartwheel” is located inside the centriole, and also has a nine fold symmetry; it includes a central suspension – the “hub” of the wheel – from which nine “spokes” are radially distributed. At their extremities, each spoke combines with one of the nine triplets of microtubules.
This cartwheel structure is a determining factor in the formation of centrioles. The resulting symmetry is essential to the functioning of the centrioles, but also to that of their extensions, the cilia and flagella. Until now, the way the symmetry actually develops has remained a mystery.
Auto-organization as a principle of construction
To resolve this enigma, the teams of Pierre Gönczy at EPFL and Michel Steinmetz at the Paul Scherrer Institute focused on a protein called SAS-6, which they knew was essential to the formation of centrioles. They discovered that this protein had the ability to combine with its “peers”: thus, two molecules of SAS-6 can join together to form what is called a “dimer”. Then, nine dimers join together to form an oligomer, which exists in the form of a “hub” from which nine “spokes” are radially distributed.
“In our model of the formation of centrioles, SAS-6 is the central element of symmetry and construction”, explains Michel Steinmetz. “It creates by itself the cartwheels, which in turn act as a foundation and skeleton of the centriole being formed. Nature has found a solution of an astonishing simplicity for a highly complex structure.”
A starting-point for new treatments
Knowledge of the symmetry of centrioles is still only at the fundamental research stage, but it already gives us a glimpse of new clinical perspectives. Defective centrioles are in fact the basis of many illnesses: as well as masculine sterility, there are various ciliar illnesses that affect the airways. “Given that the centrioles are involved in many cell processes and important body functions – from the preservation of the stability of the genome during cell division to the movement of spermatozoa – they also constitute potential targets for new active pharmaceutical ingredients. In particular, they could play a part in the development of new treatments for cancer.”