Cilia are present on most cells in the human body. These structures are typically sensory organelles, and are involved in many critical aspects of cell biology and development. The photoreceptor sensory cilium (PSC) elaborated by each rod and cone photoreceptor cell of the retina is a classic example (Figure 1). Consistent with the importance of cilia in biology, mutations in genes that encode cilia components are common causes of disease. Mutations that cause inherited retinal degenerations, which are common causes of blindness, have been identified in genes encoding more than 40 PSC proteins to date. These disorders are characterized by PSC dysfunction, followed by degeneration and death of the photoreceptor cells, resulting in loss of vision.

We are interested in studying how photoreceptor sensory cilia are built and maintained, and how these processes are disrupted in disease. For example, while there has been notable progress identifying the genetic causes of inherited retinal degenerations and other cilia disorders, the genes that harbor mutations which cause disease in half of patients with inherited retinal degeneration remain to be identified. To help understand PSCs better, and facilitate identification of new retinal degeneration disease genes, we performed a series of proteomic analyses to identify all of the proteins in mouse photoreceptor sensory cilia. The results show that PSCs are made of almost 2000 proteins, including ~1500 proteins not detected in cilia from lower organisms. This database of PSC proteins has already proved to be very useful. For example, in the past year we have used the list of genes that encode novel PSC proteins to help identify one confirmed and four potential new retinal degeneration disease genes.