Photoreceptor sensory cilia and inherited retinal degeneration

The outer segments of photoreceptor cells are specialized sensory cilia, and share many features with other primary and sensory cilia. Like other cilia, photoreceptor sensory cilium (PSC) comprises a membrane domain of outer segment and its cytoskeleton. We have recently identified the protein components of mouse PSCs, and found that the list of PSC proteins, called the PSC proteome, contains many novel cilia proteins. Studies have shown that many of the identified retinal degeneration disease genes encode proteins which are part of the PSC. Furthermore, mutations in genes encoding proteins expressed both in photoreceptors and other cilia result in systemic diseases, such as Usher syndrome, Bardet-Biedl syndrome (BBS), and Senior-Loken syndrome that involve retinal degeneration along with other disorders consequent to cilia dysfunction such as deafness and polycystic kidney disease. Based on these findings, we hypothesize that genes that encode proteins required for formation of PSCs are good candidate retinal degeneration disease genes. This chapter will summarize our studies on identifying novel PSC proteins from the PSC proteome. As an example of these studies, we demonstrated that tetratricopeptide the repeat domain 21B (TTC21B) protein is a novel PSC protein and is required for normal cilia formation in primary and photoreceptor sensory cilia.