Research

A molecular solution to centrosome structure and function

Genetic and molecular approaches have identified numerous components of the centrosomes. Thus far our knowledge of where, when and how these proteins are assembled represents just the tip of an iceberg. One major goal of our research is to assemble a dynamic 3D landscape of the centrosome pinpointing the spatial-temporal organization of its individual structural components in dividing and differentiating cells. We are using various super-resolution microscopy as the size of the centrosome is at the diffraction limit for conventional light microscopy. Knowledge of the order in which centrosome components are loaded and their spatial organization provides an important indication of the role of particular proteins and how this is governed by its molecular interactions.

Figure 1. Architectural arrangements of centrosome under sub-diffraction resolution. (A) Left and middle: Drosophila centrosome stained for Dplp and resolved by conventional (conv) or 3D-SIM mode. Right: centrosome resolved by electron microscopy (EM). Bars, 200 nm. (B,C) Different staining patterns of centrosome components (B), which is summarized in (C).

Full text: http://rsob.royalsocietypublishing.org/content/2/8/120104.long

Centriole maturation to motherhood – competent to duplicate and recruit PCM

The centriole duplicates once every cell cycle in concert with the DNA duplication. The newly assembled daughter centriole gradually recruits its components and eventually gains the ability to become the mother. We are interested in how this process takes place and how it is regulated. Our recent finding showed that in both Drosophila and human cells, three molecules Cep135, Ana1/Cep295 and Asl/Cep152 are sequentially loaded onto daughter centrioles from late interphase to mitosis, and constitute an architectural network that is key for centriole to mature to motherhood. Notably, the three molecules show an elongated distribution and interact through adjacent regions to generate a molecular network spanning from the inner- to the outer-most parts of the centriole. Ana1 provides a molecular link between the inner and outer parts of the centriole, and positions Asl at an appropriate radial position. Asl, in turn, is the recruiting partner of the master regulator of centriole duplication, Plk4, and also needed to recruit PCM. This finding accounts for the final stages in the assembly of the daughter centriole that convert it into a mature mother able to duplicate and recruit PCM.

Figure 2. Sequential loading of centrosome proteins to daughter centriole to facilitate its conversion to mature mother in Drosophila cultured cells (A). Also note the spatial distribution of these factors (B). Bar, 500 nm.

Full text: https://www.nature.com/articles/ncb3274