title: RD3: a challenge and a promise.
abstract: Photoreceptor (PR) cells are highly specialized cells that convert light into electrical signals. Ten percent of their outer segment (OS) membranes (approximately 77 cm2of membrane) are renewed every day. Therefore, PR cells must possess an extraordinary trafficking system to provide all of the needed material to build up the OS discs through a 0.3 µm diameter connecting cilium. The mechanism of trafficking of membrane proteins in the retina and corresponding degenerative diseases is still elusive. The retinal degeneration(rd3) is the gene responsible for a murine autosomal recessive hereditary retinal degeneration, which is known as Leber Congenital Amaurosis 12 (LCA12). Degeneration starts at about two weeks of age and is completed between 2-4 months. We generated the first antibody against this protein and by a protein-protein interaction analysis discovered that RD3 protein directly interacts with guanylate cyclase 1 (GC1) and partially expresses in the OS. We also detected the major binding site between these two proteins and realized that RD3 is directly involved in trafficking of this crucial protein. In a separate study, we reported that RD3 negatively regulates GC1, which is crucial for efficient trafficking of GC1 during the trafficking path, and RD3 prevents unnecessary production of cGMP. It is possible that RD3 is still involved in regulating GC1 even after targeting. Several mutations that cause visual difficulties have been reported for the mouse and human ortholog of RD3. The symptoms these mutations cause are very similar to those reported for a more severe form of blindness referred to as LCA1. Therefore, RD3 might cause a broader range of retinal diseases. Gene replacement of RD3 has shown to restore the GC1 across the retina. This makes RD3 a novel therapeutic target for retinal targeting impaired degenerative diseases.
authors: Department of Ophthalmology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, 73104, USA.
authors: Seifollah
authors: S
authors: Azadi
keywords: Guanylate cyclase1; LCA12; Leber Congenital Amaurosis 1 (LCA1); Protein trafficking; Retina; Retina degeneration3