Structural studies on CEP290, the ciliary gatekeeper

Cilia are the antennae of eukaryotic cells. They project from the apical surface of most eukaryotic cells and they are able to sense and transduce environmental signals from sources, such as light, molecules, proteins and fluid flow. The cilium possesses a distinct protein and lipid composition relative to the rest of the cell. This compartmentalisation is maintained by a structure at  the base of the cilium called the transition zone (TZ) which acts as a selectively permeable barrier to control the exchange of material between the cilium and the rest of the cell. The TZ comprises more than 20 polypeptide species. Mutations in TZ genes result in a number of inherited disorders characterised by retinal, renal and cerebral pathologies. However, the molecular mechanisms underlying these diseases are elusive because we lack a basic understanding of the structure and function of the TZ and most of its constituent proteins.

CEP290 is a major structural component of the TZ3 and is reported to bind to a number of other TZ components. For this proposal I will perform a structural and biochemical investigation into CEP290.

This research will give us a basic understanding of the structure and function of the TZ molecule.