Mark van Breugel
Structure and assembly mechanisms of centrioles
Centrioles are large and complex cell organelles that form the core of centrosomes and are essential for templating cilia and flagella. These structures are important for many cellular functions like cell division, fluid movement, motility, and sensing. Thus, it is not surprising that centriole dysfunction is associated with many human diseases such as microcephaly, ciliopathies and also cancer and infertility.
In the past many centriole components have been identified by genetic, cell biological and biochemical methods, but how they come together to make functional centrioles is an unresolved question. The architecture of centrioles has so far been studied by low-resolution methods. These showed centrioles to be 9-fold symmetric, barrel-shaped structures with the centriole wall built of microtubule triplets (Figure 1). My lab aims to elucidate how the centriolar components build-up centrioles and what precise role these components have in proper centriole functioning.
Using a combination of cell biology, biochemistry and X-ray crystallography, we recently showed how a critical assembly intermediate of centrioles is organised and how this contributes to the establishment of the 9-fold symmetry of centrioles (Figure 1). Our goal is now to understand how the centriolar assembly is extended from this intermediate and what the other important centriolar components do in this process.