The objective of this proposal is to understand the function of a small photoreceptor disc protein called PRCD. Progressive rod-cone degeneration (prcd) is an autosomal recessive retinal disease first discovered in dog and caused by a single point mutation in the PRCD gene. Mutations in the PRCD gene have been identified in human patients diagnosed with retinitis pigmentosa, including the exact mutation that causes disease in dogs. Our laboratory discovered that PRCD is uniquely localized to the light-sensitive outer segment compartment of photoreceptor cells. My preliminary data indicate that PRCD is a binding partner of rhodopsin, and that photoreceptors degenerate in the absence of PRCD in a similar manner to that seen in dogs containing a mutation in the protein.
The first aim of this proposal is to complete the characterization of the PRCD- rhodopsin interaction, and to identify additional binding partners.
The second aim i s a complete functional analysis of the PRCD knockout mouse.
These specific aims test the hypothesis that PRCD is essential for rhodopsin signaling in addition to elucidating any other functions or pathways PRCD may be involved in in photoreceptors. The importance of this work is emphasized by the fact that mutations in the protein cause blindness in both human and veterinary patients.
A single point mutation in the PRCD gene is one of the most common causes of inherited blindness in dogs, and this exact mutation along with four additional mutations have been identified in human patients diagnosed with retinitis pigmentosa. This protein is essential for photoreceptor viability, yet we know nothing about its function.
| Salinas, Raquel Y; Pearring, Jillian N; Ding, Jin-Dong et al. (2017) Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release. J Cell Biol 216:1489-1499 |
| Spencer, William J; Pearring, Jillian N; Salinas, Raquel Y et al. (2016) Progressive Rod-Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation and Rhodopsin Binding for Photoreceptor Outer Segment Localization and Maintaining Intracellular Stability. Biochemistry 55:5028-37 |
| Pearring, Jillian N; Spencer, William J; Lieu, Eric C et al. (2015) Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking. Elife 4: |
