Salje Medal - Inside the Human Cell by Dr Valentina Quarantotti

Congratulations to another Clare Hall graduate, Dr Valentina Quarantotti, who was also recently awarded a Salje Medal for her PhD in Medical Science entitled Towards the Understanding of Pericentriolar Satellite Biology. Dr Quarantotti explains more about her research here.


My PhD explores the biological function of mysterious cellular components called centriolar satellites. The name of these structures derives from the observation made on their continuous movement, reminiscent of satellites in orbit, around two intriguing cellular compartments, the centrosome and the primary cilium. Both centrosomes and cilia form from a structure called the centriole and are made up of hundreds of proteins that perform many functions within the cells. In particular, the centrosome is a cellular entity that plays an essential function in coordinating the error-free division of each cell, whereas primary cilia are antenna-like structures located on the cell surface that sense a variety of mechanical and chemical signals from the cell’s environment. Due to the fundamental roles of these compartments, centrosome and cilia abnormalities are widespread in human cancers and can also cause the onset of developmental disorders.

Centriolar satellites were first described over half a century ago. Despite multiple studies over these years which recognised satellites as potentially important cellular structures, their overall content and function remained unclear. To understand the role of centriolar satellites, I decided to first find out the molecular composition of these enigmatic structures. To this end, I established a highly specific process to isolate and purify centriolar satellites from vertebrate cells. The analysis revealed that over two hundred proteins associate with these structures and, surprisingly, that almost all the components of centrioles and centrosomes were identified in satellites. Moreover, the very same set of centrosomal proteins was present in centriolar satellites captured from cells that were engineered to lack centrosomes, suggesting that despite the large overlap in protein composition, centriolar satellites form independently of centrosomes. This study, therefore, implies that although centriolar satellites originated later in evolution than centrosomes and cilia, by harbouring a highly similar protein content, they could facilitate centrosome and cilia function in rapidly changing cellular environments, for instance during development, stress response and tissue homeostasis.


Figure 1

Representative immunofluorescence images of two human cell lines (HeLa: upper panel; RPE-1: lower panel), showing the localisation of centriolar satellites orbiting around the centrosome in each cell.

 

Figure 2

Schematic representation of centriolar satellite distribution in dividing and non-dividing cells. Centriolar satellites orbit around centrosomes and cilia. This can happen because, thanks to a motor protein called dynein, centriolar satellites associate and move along microtubules, cellular tracks involved in transport and trafficking of several cellular components. Note that a protein called PCM1 is highlighted as it is the main centriolar satellite constituent. Since satellites, centrioles and centrosomes harbour a highly similar protein content, satellites could facilitate centrosome and cilia function in rapidly changing cellular environments, for instance during development, stress response and tissue homeostasis.