PhD defence: Centrosome Formation and Function: From self-assembly of pericentriolar material to microtubule organization

The centrosome is the main microtubule organizing center (MTOC) in animal cells. It consists of a pair of centrioles which are composed of highly stable microtubules and are surrounded by pericentriolar material (PCM) that nucleates and anchors microtubules.

In this thesis, we demonstrated that self-clustering of PCM proteins is sufficient to form a compact MTOC in the absence of centrioles and thus organize a dense radial microtubule array in interphase cells. We showed that self-clustering of PCM is dynein-dependent, requires pericentrin, CDK5RAP2, ninein and γ-tubulin, but not CEP192, NEDD1 and CEP152, and can be inhibited by non-centrosomal MTOC pathways.

We have also comprehensively and systematically analyzed the role of different γ-tubulin ring complex (γ-TuRC) adaptors in cells lacking the non-centrosomal microtubule minus-end stabilization pathways and showed that γ-TuRC adaptors exert additive effects on microtubule nucleation and attachment at the centrosome. Our results support the existence of at least partially separate centrosomal pathways for γ-TuRC recruitment, microtubule nucleation and anchoring.

We also explored the function of centriole cap proteins CPAP and CP110 in centriole formation and elongation and demonstrated that the interaction between them is not essential for centriole formation but promotes centriole elongation. Together, our studies contributed to the understanding of the formation and function of the centrosome in cells.