Not So Hot Rods: Mutations in Rhodopsin Kinase in Regards to Oguchi Disease

Abstract

The average person's eyes adapt to darkness within minutes. For those with Oguchi's disease, adaptation can be slowed to several hours. Oguchi disease is an autosomal recessive disorder that results in greatly slowed phototransduction. Phototransduction is a cascade reaction beginning with a photon activating rhodopsin in the rod and leading to hyperpolarization of the cell. Oguchi disease is caused by mutations in rhodopsin kinase which prevent the phosphorylation of rhodopsin, lowering rhodopsin's affinity for arrestin. This reduced ability to bind arrestin decreases the speed in which rhodopsin is deactivated and prepped to reactivate. After a long period in a dark environment, the rhodopsin is eventually deactivated by arrestin, allowing it to be recycled. The Hartford Union High School SMART (Students Modelling a Research Topic) Team has designed a model of rhodopsin kinase to investigate its structure‐function relationship. Oguchi disease can be caused by two different mutations in rhodopsin kinase: large deletion or point mutation. In our 3D model, we will highlight the complete deletion of exon five, the partial deletion at the C‐terminus, and point mutations in the catalytic domain (Val380Asp and Pro391His) that cause Oguchi disease. Understanding the structure‐function relationships of rhodopsin kinase could shed more light on night blindness. This program is supported by a grant from NIH and CTSA.